WO2025199352A2 - Antibodies specific for solute carrier family 34 member 2 (slc34a2) - Google Patents

Abstract

Provided are Solute Carrier Family 34 Member 2 (SLC34A2)-binding molecules, in particular, antibodies specific for SLC34A2, including antibody fragments.

Description

ANTIBODIES SPECIFIC FOR SOLUTE CARRIER FAMILY 34 MEMBER 2 (SLC34A2)

Cross-Reference to Related Applications

[0001] This application claims priority from U.S. provisional application No. 63/567,864, filed March 20, 2024, entitled “ANTIBODIES SPECIFIC FOR SOLUTE CARRIER FAMILY 34 MEMBER 2 (SLC34A2),” the contents of which is incorporated by reference in its entirety.

Incorporation by Reference of Sequence Listing

[0002] This present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled 735042029240SeqList.xml, created March 20, 2025, which is 1,697,717 bytes in size. The information in the electronic format of the Sequence Listing is incorporated by reference in its entirety.

Field

[0003] The present disclosure provides novel antibodies and antigen-binding fragments thereof that bind Solute Carrier Family 34 Member 2 (SLC34A2).

Background

[0004] The Solute Carrier (SLC) family comprises three sodium-dependent phosphate transporters that play a role in the regulation of phosphate homeostasis. The three family members include Solute Carrier Family 34 Member 1 (SLC34A1; a type Ila cotransporter), SLC34A2 (a type lib cotransporter), and SLC34A3 (a type lie cotransporter). SLC34A1 and SLC34A3 are expressed in the kidneys. SLC34A2 is highly and broadly expressed, with expression being confirmed in lung, pancreas, kidney, small intestine, ovary, testis, prostate and mammary gland.

[0005] SLC34A2 expression has been reported to be altered in various cancers including but not limited to ovarian cancer, lung cancer, gastric cancer, thyroid cancer. Thus, SLC34A2 represents a potential therapeutic target for antibody-based therapies, which have proven effective treatments for several diseases. The present invention relates to use of SLC34A2, and specifically SLC34A2 proteins, in generating antibodies for use in a therapy. Summary

[0006] In some aspects, provided herein is an antibody or antigen-binding fragment thereof that binds Solute Carrier Family 34 Member 2 (SLC34A2), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein (i) the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR- H3) each having a sequence that is contained within SEQ ID NO:1 or SEQ ID NO: 161, and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) each having a sequence that is contained within SEQ ID NO:5 or SEQ ID NO: 162; (ii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 9 or SEQ ID NO: 163, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 13 or SEQ ID NO: 164; (iii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 15 or SEQ ID NO: 165, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 19 or SEQ ID NO: 154; (iv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:23 or SEQ ID NO: 166, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:27 or SEQ ID NO: 167; (v) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:31 or SEQ ID NO: 168, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:35 or SEQ ID NO:155;(vi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:39 or SEQ ID NO: 169, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:43 or SEQ ID NO: 156; (vii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:47 or SEQ ID NO: 170, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:51 or SEQ ID NO: 171; (viii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:53 or SEQ ID NO: 172, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:56 or SEQ ID NO: 173; (ix) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:59 or SEQ ID NO: 174, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:63 or SEQ ID NO: 157; (x) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:66 or SEQ ID NO: 175, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:70 or SEQ ID NO: 158; (xi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:73 or SEQ ID NO: 176, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:76 or SEQ ID NO: 177; (xii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:78 or SEQ ID NO: 178, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:82 or SEQ ID NO: 179; (xiii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:84 or SEQ ID NO: 180, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:88 or SEQ ID NO: 181; (xiv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:90 or SEQ ID NO: 182, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:93 or SEQ ID NO: 183; (xv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:94 or SEQ ID NO: 184, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:97 or SEQ ID NO:159; or (xvi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 100 or SEQ ID NO: 185, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 103 or SEQ ID NO: 160.

[0007] In some embodiments, each CDR is defined in accordance with the Kabat definition, the Chothia definition, the combination of the Kabat and the Chothia definition, the AbM definition, or the contact definition.

[0008] In some aspects, provided herein is an antibody or antigen-binding fragment thereof that specifically binds Solute Carrier Family 34 Member 2 (SLC34A2), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein: (i) the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR- H3) comprising the sequences set forth in SEQ ID NOS: 2, 3, and 4, respectively, and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) comprising the sequences set forth in SEQ ID NOS: 6, 7, and 8, respectively;(ii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 11, and 12, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7 and 14, respectively; (iii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 16, 17 and 18, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 20, 21 and 22, respectively; (iv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 24, 25 and 26, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 28, 29 and 30, respectively; (v) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 32, 33 and 34, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 37 and 38, respectively; (vi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 40, 41 and 42, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 44, 45 and 46, respectively; (vii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 48, 49 and 50, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 186 and 52, respectively; (viii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 48, 54 and 55, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 57 and 58, respectively;

(ix) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 60, 61 and 62, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 64, 21 and 65, respectively; (x) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 67, 68 and 69, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 28, 71 and 72, respectively; (xi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 32, 74 and 75, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 187, 186 and 77, respectively; (xii) the VH region comprises a CDR-H1, a CDR- H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 79, 80 and 81, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 186 and 83, respectively; (xiii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 85, 86 and 87, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 89, 21 and 65, respectively; (xiv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 91 and 92, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7 and 8, respectively; (xv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 95, 3 and 96, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 98 and 99, respectively; or (xvi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 101, 102 and 96, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 187, 104 and 105, respectively.

[0009] In some embodiments: (i) the VH region comprises an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 161, and the VL region comprises an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 5 or SEQ ID NO: 162; (ii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 9 or SEQ ID NO: 163, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 13 or SEQ ID NO: 164; (iii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 15 or SEQ ID NO: 165, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 19 or SEQ ID NO: 154; (iv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 23 or SEQ ID NO: 166, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 27 or SEQ ID NO: 167; (v) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 31 or SEQ ID NO: 168, and the V_L region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 35 or SEQ ID NO: 155; (vi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 39 or SEQ ID NO: 169, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 43 or SEQ ID NO: 156; (vii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 47 or SEQ ID NO: 170, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 51 or SEQ ID NO: 171; (viii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 53 or SEQ ID NO: 172, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 56 or SEQ ID NO: 173; (ix) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 59 or SEQ ID NO: 174, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 63 or SEQ ID NO: 157; (x) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 66 or SEQ ID NO: 175, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 70 or SEQ ID NO: 15; (xi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 73 or SEQ ID NO: 176, and the V_L region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 76 or SEQ ID NO: 177; (xii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 78 or SEQ ID NO: 178, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 82 or SEQ ID NO: 179; (xiii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 84 or SEQ ID NO: 180, and the V_L region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 88 or SEQ ID NO: 181; (xiv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 90 or SEQ ID NO: 182, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 93 or SEQ ID NO: 183; (xv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 94 or SEQ ID NO: 184, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 97 or SEQ ID NO: 159; or (xvi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 100 or SEQ ID NO: 185, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 103 or SEQ ID NO: 160.

[0010] In some aspects, provided herein is an antibody or antigen-binding fragment thereof that specifically binds Solute Carrier Family 34 Member 2 (SLC34A2), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein: (i) the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR- H3) comprising the sequences set forth in SEQ ID NOS: 2, 3, and 4, respectively, and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) comprising the sequences set forth in SEQ ID NOS: 6, 7, and 8, respectively; (ii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 11, and 12, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7 and 14, respectively; (iii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 16, 17 and 18, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 20, 21 and 22, respectively; (iv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 24, 25 and 26, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 28, 29 and 30, respectively; (v) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 32, 33 and 34, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 37 and 38, respectively; (vi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 40, 41 and 42, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 44, 45 and 46, respectively; (vii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 48, 49 and 50, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 186 and 52, respectively; (viii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 48, 54 and 55, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 57 and 58, respectively; (ix) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 60, 61 and 62, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 64, 21 and 65, respectively; (x) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 67, 68 and 69, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 28, 71 and 72, respectively; (xi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 32, 74 and 75, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 187, 186 and 77, respectively; (xii) the VH region comprises a CDR-H1, a CDR- H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 79, 80 and 81, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 186 and 83, respectively; (xiii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 85, 86 and 87, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 89, 21 and 65, respectively; (xiv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 91 and 92, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7 and 8, respectively; (xv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 95, 3 and 96, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 98 and 99, respectively; or (xvi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 101, 102 and 96, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 187, 104 and 105, respectively.

[0011] In some embodiments: (i) the VH region comprises an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 161, and the VL region comprises an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 5 or SEQ ID NO: 162; (ii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 9 or SEQ ID NO: 163, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 13 or SEQ ID NO: 164; (iii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 15 or SEQ ID NO: 165, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 19 or SEQ ID NO: 154; (iv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 23 or SEQ ID NO: 166, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 27 or SEQ ID NO: 167; (v) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 31 or SEQ ID NO: 168, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 35 or SEQ ID NO: 155; (vi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 39 or SEQ ID NO: 169, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 43 or SEQ ID NO: 156; (vii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 47 or SEQ ID NO: 170, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 51 or SEQ ID NO: 171; (viii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 53 or SEQ ID NO: 172, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 56 or SEQ ID NO: 173; (ix) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 59 or SEQ ID NO: 174, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 63 or SEQ ID NO: 157; (x) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 66 or SEQ ID NO: 175, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 70 or SEQ ID NO: 158; (xi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 73 or SEQ ID NO: 176, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 76 or SEQ ID NO: 177; (xii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 78 or SEQ ID NO: 178, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 82 or SEQ ID NO: 179; (xiii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 84 or SEQ ID NO: 180, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 88 or SEQ ID NO: 181; (xiv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 90 or SEQ ID NO: 182, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 93 or SEQ ID NO: 183; (xv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 94 or SEQ ID NO: 184, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 97 or SEQ ID NO: 159; or (xvi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 100 or SEQ ID NO: 185, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 103 or SEQ ID NO: 160.

[0012] In some embodiments: (i) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 1 or 161 and 5 or 162, respectively; (ii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 9 or 163 and 13 or 164, respectively; (iii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 15 or 165 and 19 or 154, respectively; (iv) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 23 or 166 and 27 or 167, respectively; (v) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 31 or 168 and 35 or 155, respectively; (vi) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 39 or 169 and 43 or 156, respectively; (vii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 47 or 170 and 51 or 171, respectively; (viii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 53 or 172 and 56 or 173, respectively; (ix) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 59 or 174 and 63 or 157, respectively; (x) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 66 or 175 and 70 or 158, respectively; (xi) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 73 or 176 and 76 or 177, respectively; (xii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 78 or 178 and 82 or 179, respectively; (xiii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 84 or 180 and 88 or 181, respectively; (xiv) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 90 or 182 and 93 or 183, respectively; (xv) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 94 or 184 and 97 or 159, respectively; or (xvi) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 100 or 185 and 103 or 160, respectively.

[0013] In some embodiments, the antibody is a full-length antibody. In some embodiments, the heavy chain further comprises a constant domain of a human immunoglobulin heavy chain and the light chain further comprises a constant domain of a human light chain. In some embodiments, the constant domain of a human immunoglobulin heavy chain is from a IgGl heavy chain. In some embodiments, the constant domain of a human immunoglobulin heavy chain comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 113. In some embodiments, the constant domain of a human immunoglobulin heavy chain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the constant domain of a human light chain is from a human kappa light chain. In some embodiments, the constant domain of a human light chain comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 114. In some embodiments, the constant domain of a human light chain comprises the amino acid sequence of SEQ ID NO: 114. In some embodiments, the full-length antibody comprises a heavy chain constant domain comprising the amino acid sequence of SEQ ID NO: 113, and a light chain constant domain comprising the amino acid sequence of SEQ ID NO: 114.

[0014] In some embodiments, the antibody is an antigen-binding fragment. In some embodiments, the antigen-binding fragment is a Fab. In some embodiments, the antigen-binding fragment thereof comprises a single chain variable fragment (scFv). In some embodiments, the VH is amino-terminal to VL. In some embodiments, the VH is carboxy-terminal to VL. [0015] In some embodiments, the antibody or antigen-binding fragment thereof is monoclonal. In some embodiments, the antibody or antigen-binding fragment thereof is recombinant. In some embodiments, the VH and VL are human or are derived from a human protein. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to a human SLC34A2 protein. In some embodiments, the human SLC34A2 protein is set forth by the amino acid sequence of SEQ ID NO: 108. In some embodiments, the human SLC34A2 protein is set forth by the amino acid sequence of SEQ ID NO: 111. In some embodiments, the human SLC34A2 protein is set forth by the amino acid sequence of SEQ ID NO:115.

[0016] In some embodiments, the EC50 value of binding to human SLC34A2 protein is in the range of about 5 to 50 nM. In some embodiments, the EC50 value is less than 15 nM. In some embodiments, the EC50 value is based on binding to SLC34A2 expressed on OVCAR3 cells.

[0017] In some aspects, provided herein is a conjugate, comprising any of the SLC34A2 antibody or antigen-binding fragments thereof provided herein, and a heterologous moiety.

[0018] In some aspects, provided herein is a synthetic receptor, comprising an extracellular antigen-binding domain comprising any of the antibody or antigen-binding fragments thereof provided herein. In some embodiments, the synthetic receptor is a chimeric antigen receptor (CAR) further comprising a spacer, transmembrane domain, and an intracellular signaling domain. In some aspects, provided herein is a chimeric antigen receptor (CAR), comprising an extracellular antigen-binding domain comprising any of the antibody or antigen-binding fragments thereof provided herein, a spacer, transmembrane domain, and an intracellular signaling domain. In some aspects, provided herein is a synthetic receptor comprising from N- terminus to C-terminus an extracellular antigen-binding domain comprising any of the antibody or antigen-binding fragments thereof provided herein, a transmembrane domain, and an intracellular domain comprising transcriptional effector. In some embodiments, the intracellular domain is a human or humanized transcriptional effector.

[0019] In some aspects, provided herein is a nucleic acid molecule(s) encoding the heavy chain and/or the light chain of any of the antibody or antigen-binding fragments thereof provided herein. In some aspects, provided herein is a vector comprising any of the nucleic acids provided herein.

[0020] In some embodiments, the vector is an expression vector.

[0021] In some aspects, provided herein is a host cell comprising any of the nucleic acids or any of the vectors provided herein. In some embodiments, the host cell is a mammalian cell. [0022] In some aspects, provided herein is a method of producing an antibody or antigenbinding fragment thereof comprising culturing any of the host cells provided herein under a condition that produces the antibody or antigen-binding fragment thereof. In some embodiments, the method further comprises recovering the antibody or antigen-binding fragment thereof produced by the host cell. In some aspects, provided herein is an antibody or antigen-binding fragment thereof produced by any of the methods provided herein.

[0023] In some aspects, provided herein is a composition comprising any of the antibody or antigen-binding fragment thereof provided herein, any of the conjugates provided herein, any of the synthetic receptors provided herein, any of the CARs provided herein, or any of the compositions provided herein. In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

[0024] In some aspects, provided herein is a method of treatment, comprising administering any of the antibody or antigen-binding fragment thereof provided herein, any of the conjugates provided herein, any of the synthetic receptors provided herein, any of the CARs provided herein, or any of the compositions provided herein, to a subject having a disease or disorder. In some embodiments, the disease or disorder is a cancer, optionally ovarian cancer. In some embodiments, the subject is a human.

[0025] In some aspects, provided herein is use of any of the compositions provided herein for the manufacture of a medicament for treatment of a disease or disorder. In some aspects, provided herein is use of any of the compositions provided herein for treatment of a disease or disorder. In some embodiments, the disease or disorder is a cancer, optionally ovarian cancer. In some embodiments, the composition is for use in treatment of a disease or disorder. In some embodiments the disease or disorder is a cancer, optionally ovarian cancer.

Detailed Description

[0026] Among the provided embodiments are antibodies and antigen-binding fragments thereof, including SLC34A2-binding antibodies, nucleic acid molecules that encode SLC34A2- binding antibodies, and compositions and articles of manufacture comprising the same. The antibodies generally can contain heavy chain variable (VH) regions and light chain variable (VL) regions. The VH region can contain a heavy chain complementarity determining region 1 (CDR- Hl), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3). The VL region can contain a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3). Also provided are methods of making SLC34A2-binding antibodies.

[0027] All publications, including patent documents, scientific articles and databases, referred to in this application are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication were individually incorporated by reference. If a definition set forth herein is contrary to or otherwise inconsistent with a definition set forth in the patents, applications, published applications and other publications that are herein incorporated by reference, the definition set forth herein prevails over the definition that is incorporated herein by reference.

[0028] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

I. DEFINITIONS

[0029] Unless defined otherwise, all terms of art, notations and other technical and scientific terms or terminology used herein are intended to have the same meaning as is commonly understood by one of ordinary skill in the art to which the claimed subject matter pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art.

[0030] It is understood that embodiments of the invention described herein include “consisting of’ and/or “consisting essentially of’ embodiments. As used herein, the singular form “a”, “an”, and “the” includes plural references unless indicated otherwise. Use of the term “or” herein is not meant to imply that alternatives are mutually exclusive.

[0031] In this application, the use of “or” means “and/or” unless expressly stated or understood by one skilled in the art. In the context of a multiple dependent claim, the use of “or” refers back to more than one preceding independent or dependent claim.

[0032] The term “about” as used herein refers to the usual error range for the respective value readily known to the skilled person in this technical field. Reference to “about” a value or parameter herein includes (and describes) embodiments that are directed to that value or parameter per se. For example, description referring to “about X” includes description of “X”.

[0033] The term “antibody,” as used herein, refers to an immunoglobulin molecule which specifically binds with an antigen. Antibodies can be intact immunoglobulins derived from natural sources or from recombinant sources and can be immunoreactive portions of intact immunoglobulins. An intact or full-length antibody typically is a tetramer of immunoglobulin molecules comprising two heavy chain and two light chain polypeptides. Each polypeptide chain contains three complementarity-determining regions (CDRs), which bind to the antigen and defines the antibody's antigen specificity. The term “antibody” herein is used in the broadest sense and includes polyclonal and monoclonal antibodies, including intact antibodies and functional (antigen-binding) antibody fragments, including fragment antigen binding (Fab) fragments, F(ab’)2 fragments, Fab’ fragments, Fv fragments, recombinant IgG (rlgG) fragments, heavy chain variable (VH) regions capable of specifically binding the antigen, single chain antibody fragments, including single chain variable fragments (scFv), and single domain antibodies (e.g., sdAb, sdFv, nanobody, VHH) fragments. Unless otherwise stated, the term “antibody” should be understood to encompass such functional antibody fragments thereof also referred to herein as “antigen-binding fragments.” The term also encompasses intact or full- length antibodies, including antibodies of any class or sub-class, including IgG and sub-classes thereof, IgM, IgE, IgA, and IgD. An antibody or antibody fragment also includes a human antibody or a humanized antibody or a portion of a human antibody or a humanized antibody. The term encompasses genetically engineered and/or otherwise modified forms of immunoglobulins, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multispecific, e.g., bispecific or trispecific, antibodies, diabodies, triabodies, and tetrabodies, tandem di-scFv, tandem tri-scFv.

[0034] The term “variable region” or “variable domain” refers to the domain of an antibody heavy or light chain that is involved in binding the antibody to antigen. The variable regions of the heavy chain and light chain (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three CDRs (See, e.g., Kindt et al. Kuby Immunology, 6th ed., W.H. Freeman and Co., page 91 (2007)). A single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind a particular antigen may be isolated using a VH or VL domain from an antibody that binds the antigen to screen a library of complementary VL or VH domains, respectively. See, e.g., Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991).

[0035] The terms “complementarity determining region,” and “CDR,” synonymous with “hypervariable region” or “HVR,” are known to refer to non-contiguous sequences of amino acids within antibody variable regions, which confer antigen specificity and/or binding affinity. In general, there are three CDRs in each heavy chain variable region (CDR-H1, CDR-H2, CDR- H3) and three CDRs in each light chain variable region (CDR-L1, CDR-L2, CDR-L3). “Framework regions” and “FR” are known to refer to the non-CDR portions of the variable regions of the heavy and light chains. In general, there are four FRs in each full-length heavy chain variable region (FR-H1, FR-H2, FR-H3, and FR-H4), and four FRs in each full-length light chain variable region (FR-L1, FR-L2, FR-L3, and FR-L4). Methods of determining and identifying CDRs and boundaries with FRs can be determined according to known schemes, such as described herein (e.g., Table 2).

[0036] The term “monoclonal antibody” as used herein refers to an antibody obtained from or within a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical, except for possible variants containing naturally occurring mutations or arising during production of a monoclonal antibody preparation, such variants generally being present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different epitopes, each monoclonal antibody of a monoclonal antibody preparation is directed against a single epitope on an antigen. The term is not to be construed as requiring production of the antibody by any particular method. A monoclonal antibody may be made by a variety of techniques, including but not limited to generation from a hybridoma, recombinant DNA methods, phage-display and other antibody display methods.

[0037] The term “humanized” with reference to an antibody or antigen-binding fragment refers to chimeric antibodies that contain minimal sequence derived from a non-human immunoglobulin. Generally, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a hypervariable region (complementarity determining region or CDR) of the recipient are replaced by residues from a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit or nonhuman primate having the desired specificity, affinity, and capacity. In some instances, framework region (FR) residues of the human immunoglobulin (recipient antibody) are replaced by corresponding non-human residues of the donor antibody. Typically, humanized forms of non-human (e.g., murine) antibodies include substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin sequence. Humanized antibodies may comprise residues that are not found in the recipient antibody or in the donor antibody. In general, the humanized antibody may comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops (CDRs) correspond to those of a non-human immunoglobulin (donor antibody having the desired specificity, affinity, and capacity) and all or substantially all of the FRs are those of a human immunoglobulin sequence. In one embodiment, humanized antibodies comprise a humanized FR that exhibits at least 65% sequence identity with an acceptor (non-human) FR, e.g., murine FR. The humanized antibody also may comprise at least a portion of an immunoglobulin constant region (Fc), particularly a human immunoglobulin.

[0038] As used herein, "optional" or "optionally" means that the subsequently described event or circumstance does or does not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. For example, an optionally substituted group means that the group is unsubstituted or is substituted.

[0039] The terms “nucleic acid molecule”, “nucleic acid” and “polynucleotide” may be used interchangeably, and refer to a polymer of nucleotides. Such polymers of nucleotides may contain natural and/or non-natural nucleotides, and include, but are not limited to, DNA, RNA, and PNA. “Nucleic acid sequence” refers to the linear sequence of nucleotides comprised in the nucleic acid molecule or polynucleotide.

[0040] The term “isolated” as used herein refers to a molecule that has been separated from at least some of the components with which it is typically found in nature or produced. For example, a polypeptide is referred to as “isolated” when it is separated from at least some of the components of the cell in which it was produced. Where a polypeptide is secreted by a cell after expression, physically separating the supernatant containing the polypeptide from the cell that produced it is considered to be “isolating” the polypeptide. Similarly, a polynucleotide is referred to as “isolated” when it is not part of the larger polynucleotide (such as, for example, genomic DNA or mitochondrial DNA, in the case of a DNA polynucleotide) in which it is typically found in nature, or is separated from at least some of the components of the cell in which it was produced, for example, in the case of an RNA polynucleotide. Thus, a DNA polynucleotide that is contained in a vector inside a host cell may be referred to as “isolated”.

[0041] The terms “polypeptide” and “protein” are used interchangeably to refer to a polymer of amino acid residues, and are not limited to a minimum length. Such polymers of amino acid residues may contain natural or non-natural amino acid residues, and include, but are not limited to, peptides, oligopeptides, dimers, trimers, and multimers of amino acid residues. Both full- length proteins and fragments thereof are encompassed by the definition. The terms also include post-expression modifications of the polypeptide, for example, glycosylation, sialylation, acetylation, phosphorylation, and the like. Furthermore, for purposes of the present disclosure, a “polypeptide” refers to a protein which includes modifications, such as deletions, additions, and substitutions (generally conservative in nature), to the native sequence, as long as the protein maintains the desired activity. These modifications may be deliberate, as through site-directed mutagenesis, or may be accidental, such as through mutations of hosts which produce the proteins or errors due to PCR amplification.

[0042] The term "isolated protein" referred to herein means that a subject protein (1) is free of at least some other proteins with which it would typically be found in nature, (2) is essentially free of other proteins from the same source, e.g., from the same species, (3) is expressed by a cell from a different species, (4) has been separated from at least about 50 percent of polynucleotides, lipids, carbohydrates, or other materials with which it is associated in nature, (5) is not associated (by covalent or noncovalent interaction) with portions of a protein with which the "isolated protein" is associated in nature, (6) is operably associated (by covalent or noncovalent interaction) with a polypeptide with which it is not associated in nature, or (7) does not occur in nature. Such an isolated protein can be encoded by genomic DNA, cDNA, mRNA or other RNA, of may be of synthetic origin, or any combination thereof. In certain embodiments, the isolated protein is substantially pure or substantially free from proteins or polypeptides or other contaminants that are found in its natural environment that would interfere with its use (therapeutic, diagnostic, prophylactic, research or otherwise). The term “purified” as applied to nucleic acids or proteins generally denotes a nucleic acid or polypeptide that is substantially free from other components as determined by analytical techniques well known in the art (e.g., a purified polypeptide or polynucleotide forms a discrete band in an electrophoretic gel, chromatographic eluate, and/or a media subjected to density gradient centrifugation). For example, a nucleic acid or polypeptide that gives rise to essentially one band in an electrophoretic gel is “purified.” A purified nucleic acid or protein is at least about 50% pure, usually at least about 75%, 80%, 85%, 90%, 95%, 96%, 99% or more pure (e.g., percent by weight or on a molar basis).

[0043] The term “recombinant” indicates that the material (e.g., a nucleic acid or a polypeptide) has been artificially (i.e., non-naturally) altered by human intervention. The alteration can be performed on the material within, or removed from, its natural environment or state. For example, a “recombinant nucleic acid” is one that is made by recombining nucleic acids, e.g., during cloning, affinity modification, DNA shuffling or other well-known molecular biological procedures. A “recombinant DNA molecule,” is comprised of segments of DNA joined together by means of such molecular biological techniques. The term “recombinant protein” or “recombinant polypeptide” as used herein refers to a protein molecule which is expressed using a recombinant DNA molecule. A “recombinant host cell” is a cell that contains and/or expresses a recombinant nucleic acid or that is otherwise altered by genetic engineering, such as by introducing into the cell a nucleic acid molecule encoding a recombinant protein, such as an immunomodulatory protein provided herein. Transcriptional control signals in eukaryotes comprise “promoter” and “enhancer” elements. Promoters and enhancers consist of short arrays of DNA sequences that interact specifically with cellular proteins involved in transcription. Promoter and enhancer elements have been isolated from a variety of eukaryotic sources including genes in yeast, insect and mammalian cells and viruses (analogous control elements, i.e., promoters, are also found in prokaryotes). The selection of a particular promoter and enhancer depends on what cell type is to be used to express the protein of interest.

[0044] As used herein, “substantially pure” means an object species is the predominant species present i.e., on a molar basis it is more abundant than any other individual species in the composition), and a substantially purified fraction is a composition wherein the object species comprises at least about 50 percent (on a molar basis) of all macromolecular species present. Generally, a substantially pure composition will comprise more than about 80 percent of all macromolecular species present in the composition, for example, in some embodiments, more than about 85%, 90%, 95%, and 99%. In some embodiments, the object species is purified to essential homogeneity (contaminant species cannot be detected in the composition by conventional detection methods) wherein the composition consists essentially of a single macromolecular species.

[0045] The term “substantially similar” or “substantially the same,” as used herein, denotes a sufficiently high degree of similarity between two or more numeric values such that one of skill in the art would consider the difference between the two or more values to be of little or no biological and/or statistical significance within the context of the biological characteristic measured by said value. In some embodiments the two or more substantially similar values differ by no more than about any one of 5%, 10%, 15%, 20%, 25%, or 50%.

[0046] A polypeptide “variant” means a biologically active polypeptide having at least about 80% amino acid sequence identity with the native sequence polypeptide after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Such variants include, for instance, polypeptides wherein one or more amino acid residues are added, or deleted, at the N- or C-terminus of the polypeptide. In some embodiments, a variant will have at least about 80% amino acid sequence identity. In some embodiments, a variant will have at least about 90% amino acid sequence identity. In some embodiments, a variant will have at least about 95% amino acid sequence identity with the native sequence polypeptide.

[0047] As used herein, “percent (%) amino acid sequence identity” and “homology” with respect to a peptide, polypeptide or antibody sequence are defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific peptide or polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or MEGALIGNTM (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.

[0048] An amino acid substitution may include but are not limited to the replacement of one amino acid in a polypeptide with another amino acid. Exemplary substitutions are shown in Table 1. Amino acid substitutions may be introduced into an antibody of interest and the products screened for a desired activity, for example, retained/improved antigen binding, decreased immunogenicity, or improved ADCC or CDC.

[0049] Amino acids may be grouped according to common side-chain properties:

(1) hydrophobic: Norleucine, Met, Ala, Vai, Leu, He;

(2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gin;

(3) acidic: Asp, Glu;

(4) basic: His, Lys, Arg;

(5) residues that influence chain orientation: Gly, Pro;

(6) aromatic: Trp, Tyr, Phe.

[0050] Non-conservative substitutions will entail exchanging a member of one of these classes for another class.

[0051] The term “conservative amino acid substitution” as used herein means an amino acid substitution in which an amino acid residue is substituted by another amino acid residue having a side chain R group with similar chemical properties (e.g., charge or hydrophobicity). Examples of groups of amino acids that have side chains with similar chemical properties include 1) aliphatic side chains: glycine, alanine, valine, leucine, and isoleucine; 2) aliphatic -hydroxyl side chains: serine and threonine; 3) amide-containing side chains: asparagine and glutamine; 4) aromatic side chains: phenylalanine, tyrosine, and tryptophan; 5) basic side chains: lysine, arginine, and histidine; 6) acidic side chains: aspartic acid and glutamic acid; and 7) sulfur-containing side chains: cysteine and methionine. Conservative amino acids substitution groups are: valine- leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, glutamate-aspartate, and asparagine-glutamine.

[0052] The term, “corresponding to” with reference to positions of a protein, such as recitation that nucleotides or amino acid positions “correspond to” nucleotides or amino acid positions in a disclosed sequence, such as set forth in the Sequence Listing, refers to nucleotides or amino acid positions identified upon alignment with the disclosed sequence based on structural sequence alignment or using a standard alignment algorithm, such as the GAP algorithm. By aligning the sequences, one skilled in the art can identify corresponding residues, for example, using conserved and identical amino acid residues as guides. The term “specifically binds” as used herein means the ability of a protein, under specific binding conditions, to bind to a target protein such that its affinity or avidity is at least 10 times as great, but optionally 50, 100, 250 or 500 times as great, or even at least 1000 times as great as the average affinity or avidity of the same protein to a collection of random peptides or polypeptides of sufficient statistical size. A specifically binding protein need not bind exclusively to a single target molecule but may specifically bind to more than one target molecule. In some cases, a specifically binding protein may bind to a protein that has similarity in structural conformation with the target protein (e.g., paralogs or orthologs). Those of skill will recognize that specific binding to a molecule having the same function in a different species of animal (i.e., ortholog) or to a molecule having a substantially similar epitope as the target molecule (e.g., paralog) is possible and does not detract from the specificity of binding which is determined relative to a statistically valid collection of unique non-targets (e.g., random polypeptides). Thus, a protein of the invention may specifically bind to more than one distinct species of target molecule due to cross -reactivity. Solid-phase ELISA immunoassays, ForteBio Octet or Biacore measurements can be used to determine specific binding between two proteins. Generally, interactions between two binding proteins have dissociation constants (Kd) less than about IxlO'⁵ M, and often as low as about 1 x 10'¹² M. In certain aspects of the present disclosure, interactions between two binding proteins have dissociation constants of less than about IxlO'⁶ M, IxlO'⁷ M, 1X10'⁸ M, IxlO'⁹ M, IxlO'¹⁰ M, or IxlO'¹¹ M or less.

[0053] The term “affinity” with reference to binding refers to the strength of the sum total of noncovalent interactions between a single binding site of a molecule (for example, an antibody) and its binding partner (for example, an antigen). The affinity or the apparent affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (KD) or the Ko-apparent, respectively. Affinity can be measured by common methods known in the art (such as, for example, ELISA KD, KinExA, flow cytometry, and/or surface plasmon resonance devices), including those described herein. Such methods include, but are not limited to, methods involving BIAcore®, Octet®, or flow cytometry. In some embodiments, the KD of the antigen-binding molecule is measured by flow cytometry using an antigen-expressing cell line and fitting the mean fluorescence measured at each antibody concentration to a non-linear one- site binding equation (Prism Software graphpad).

[0054] The term “vector” is used to describe a polynucleotide that can be engineered to contain a cloned polynucleotide or polynucleotides that can be propagated in a host cell. A vector can include one or more of the following elements: an origin of replication, one or more regulatory sequences (such as, for example, promoters and/or enhancers) that regulate the expression of the polypeptide of interest, and/or one or more selectable marker genes (such as, for example, antibiotic resistance genes and genes that can be used in colorimetric assays, for example, P-galactosidase). The term “expression vector” refers to a vector that is used to express a polypeptide of interest in a host cell. [0055] A “host cell” refers to a cell that may be or has been a recipient of a vector or isolated polynucleotide. Host cells may be prokaryotic cells or eukaryotic cells. Exemplary eukaryotic cells include mammalian cells, such as primate or non-primate animal cells; fungal cells, such as yeast; plant cells; and insect cells. Nonlimiting exemplary mammalian cells include, but are not limited to, NSO cells, PER.C6® cells (Crucell), and 293 and CHO cells, and their derivatives, such as 293-6E, CHO-DG44, CHO-K1, CHO-S, and CHO-DS cells. Host cells include progeny of a single host cell, and the progeny may not necessarily be completely identical (in morphology or in genomic DNA complement) to the original parent cell due to natural, accidental, or deliberate mutation. A host cell includes cells transfected in vivo with a polynucleotide(s) a provided herein.

[0056] The term “expression” refers to the process by which a polynucleotide is transcribed from a DNA template (such as into an mRNA or other RNA transcript) and/or the process by which a transcribed mRNA is subsequently translated into peptide, polypeptides or proteins. Transcripts and encoded polypeptides may be collectively referred to as “gene product.” If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in a eukaryotic cell.

[0057] The terms “individual” and “subject” are used interchangeably herein to refer to an animal; for example a mammal. The term patient includes human and veterinary subjects. In some embodiments, methods of treating mammals, including, but not limited to, humans, rodents, simians, felines, canines, equines, bovines, porcines, ovines, caprines, mammalian laboratory animals, mammalian farm animals, mammalian sport animals, and mammalian pets, are provided. The subject can be male or female and can be any suitable age, including infant, juvenile, adolescent, adult, and geriatric subjects. In some embodiments, the subject to receive the treatment can be a patient, designating the fact that the subject has been identified as having a disorder of relevance to the treatment, or being at adequate risk of contracting the disorder. In particular embodiments, the subject is a human, such as a human patient.

[0058] The term “composition” refers to any mixture of two or more products, substances, or compounds, including cells or antibodies. It may be a solution, a suspension, liquid, powder, a paste, aqueous, non-aqueous or any combination thereof. The preparation is generally in such form as to permit the biological activity of the active ingredient (e.g. antibody) to be effective.

[0059] A “pharmaceutically acceptable carrier” refers to an ingredient in a pharmaceutical formulation, other than an active ingredient, which is nontoxic to a subject. A pharmaceutically acceptable carrier includes, but is not limited to, a buffer, excipient, stabilizer, or preservative. [0060] As used herein, the term “treatment” or “treating” refers to clinical intervention designed to alter the natural course of the individual or cell being treated during the course of clinical pathology. Desirable effects of treatment include decreasing the rate of disease progression, ameliorating or palliating the disease state, and remission or improved prognosis. An individual is successfully “treated”, for example, if one or more symptoms associated with a disorder (e.g., an eosinophil-mediated disease) are mitigated or eliminated. For example, an individual is successfully “treated” if treatment results in increasing the quality of life of those suffering from a disease, decreasing the dose of other medications required for treating the disease, reducing the frequency of recurrence of the disease, lessening severity of the disease, delaying the development or progression of the disease, and/or prolonging survival of individuals.

[0061] An “effective amount” refers to at least an amount effective, at dosages and for periods of time necessary, to achieve the desired or indicated effect, including a therapeutic or prophylactic result. An effective amount can be provided in one or more administrations. A “therapeutically effective amount” is at least the minimum dose of cells required to effect a measurable improvement of a particular disorder. In some embodiments, a therapeutically effective amount is the amount of a composition that reduces the severity, the duration and/or the symptoms associated with cancer, viral infection, microbial infection, or septic shock in an animal. A therapeutically effective amount herein may vary according to factors such as the disease state, age, sex, and weight of the patient. A therapeutically effective amount may also be one in which any toxic or detrimental effects of the antibody are outweighed by the therapeutically beneficial effects. A “prophylactically effective amount” refers to an amount effective, at the dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically but not necessarily, since a prophylactic dose is used in subjects prior to or at the earlier stage of disease, the prophylactically effective amount can be less than the therapeutically effective amount.

[0062] A “disease” or “disorder” as used herein refers to a condition where treatment is needed and/or desired. In some embodiments, malignancy or dysproliferative changes (such as metaplasias and dysplasias), or hyperproliferative disorders, are treated or prevented by the methods and compositions of the invention in the ovary, bladder, breast, colon, lung, skin, pancreas, or uterus. In other specific embodiments, sarcoma, melanoma, or leukemia is treated or prevented by the methods and compositions of the invention.

[0063] As used herein, combination refers to any association between or among two or more items. The combination can be two or more separate items, such as two compositions or two collections, can be a mixture thereof, such as a single mixture of the two or more items, or any variation thereof. The elements of a combination are generally functionally associated or related.

[0064] As used herein, a kit is a packaged combination that optionally includes other elements, such as additional agents and instructions for use of the combination or elements thereof, for a purpose including, but not limited to, therapeutic uses.

[0065] The term “wild-type” or “natural” or “native,” which are used interchangeably, as used herein is used in connection with biological materials such as nucleic acid molecules, proteins, host cells, and the like, that are found in nature and not modified by human intervention.

IL SLC34A2 TARGETING ANTIBODIES

[0066] Provided herein are SLC34A2 antibodies and antigen-binding fragments thereof. In some embodiments, the antibodies or antigen-binding fragments thereof include antibodies that specifically bind to SLC34A2, e.g., human SLC34A2. Among the provided anti-SLC34A2 antibodies and antigen-binding fragments thereof are those that exhibit high affinity binding to SLC34A2 protein and SLC34A2-expressing cells.

[0067] In some aspects, provided antibodies and antigen binding fragments comprise a means for binding to a SLC34A2 protein. In some embodiments, the means binds a human SLC34A2 protein (e.g., the SLC34A2 protein of SEQ ID NO: 111) and related isoforms and orthologs. In some embodiments, a SLC34A2 antibody or antigen-binding fragment comprise means for binding a human SLC34A2 protein. In some embodiments, among provided antibodies and antigen binding fragments are any that bind SLC34A2, such as human SLC34A2, in the region(s) of human SLC34A2 bound by an SLC34A2 antibody or antigen binding fragment thereof as described in the Examples below. In some embodiments, the means is a SLC34A2 antibody or antigen-binding fragment or equivalent thereof e.g., a full length antibody or a F(ab')2 fragment, a Fab fragment, a single chain variable fragment (scFv), and a single domain antibody (sdAb), or a functional fragment thereof) means for binding a SLC34A2 protein. In some embodiments, the means for binding SLC34A2 includes the anti-SLC34A2 antibodies and antigen-binding fragments or equivalents thereof described herein.

[0068] The antibodies of the disclosure may be monoclonal, genetically engineered, and/or otherwise modified in nature, including but not limited to humanized antibodies.

[0069] In provided embodiments, an anti-SLC34A2 antibody or antigen-binding fragment provided herein is a humanized antibody or an antigen-binding fragment thereof. [0070] Among the provided antibodies are monoclonal antibodies, including monoclonal antibody fragments. In some aspects, the antibody or the antigen-binding fragments of the antibody is isolated. Also provided are SLC34A2-binding molecules containing such antibodies or antigen-binding fragments thereof, such as single-chain proteins, fusion proteins, conjugates and/or recombinant receptors such as chimeric antigen receptors.

[0071] Also provided are polynucleotides containing nucleic acids sequences encoding all or a portion of such antibodies, including an antigen-binding fragment, or binding molecule. The provided polynucleotides can be incorporated into constructs, such as deoxyribonucleic acid (DNA) or RNA constructs, such as those that can be introduced into cells for expression of the encoded anti-SLC34A2 antibodies or binding molecules.

[0072] In some embodiments, the provided anti-SLC34A2 antibodies and antigen-binding fragments thereof contain a heavy chain variable region (VH) sequence and a light chain variable region (VL) sequence as described, or a sufficient antigen-binding fragment thereof. In some embodiments, anti-SLC34A2 antibodies provided herein include complementarity determining regions (CDRs), also known as hypervariable regions, in both the VH and VL domains. In some such embodiments, the VH is the region of the anti-SLC34A2 antibody that comprises the three heavy chain complementarity determining regions (CDRs) and the VL chain is the region of the anti-SLC34A2 antibody that comprises the three light chain CDRs. Among provided anti- SLC34A2 antibodies, including full-length antibodies or antigen-binding fragments, are antibodies that contains a VH region sequence that contains a CDR-H1, a CDR-H2 and a CDR- H3 as described and contains a VL region sequence that contains a CDR-L1, a CDR-L2 and a CDR-L3 as described.

[0073] As is known in the art, the amino acid position/boundary delineating a hypervariable region of an antibody can vary, depending on the context and the various definitions known in the art. Some positions within a variable domain may be viewed as hybrid hypervariable positions in that these positions can be deemed to be within a hypervariable region under one set of criteria while being deemed to be outside a hypervariable region under a different set of criteria. One or more of these positions can also be found in extended hypervariable regions. The inventive concept provides antibodies including modifications in these hybrid hypervariable positions.

[0074] The precise amino acid sequence boundaries of a given CDR or FR can be readily determined using any of a number of well-known schemes, including those described by Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (“Kabat” numbering scheme); Al-Lazikani et al., J 1 Mol Biol, 1997; 273(4):927-48 (“Chothia” numbering scheme); MacCallum et al., J. Mol. Biol, 1996; 262:732-745.” (“Contact” numbering scheme); Lefranc MP et al., Dev Comp Immunol, 2003; 27(l):55-77 (“IMGT” numbering scheme); Honegger A and Pliickthun A, J Mol Biol, 2001; 309(3):657-70, (“Aho” numbering scheme); Martin et al., PNAS, 1989; 86(23):9268-9272, (“AbM” numbering scheme); and Ye et al., Nucleic Acids Res. 2013; 41 (Web Server issue):W34-40, (“IgBLAST numbering scheme). Details regarding various numbering schemes are also described in, for example, Jarasch et al., Proteins, 2017; 85( l):65-71 ; Martin et al., Bioinformatics tools for antibody engineering. In: Diibel, S. (editor) Handbook of Therapeutic Antibodies, Vol. 1. Wiley-VCH, Weinheim, Germany; Martin, A.C.R. (2010). Protein Sequence and Structure Analysis of Antibody Variable Domains. In: Kontermann, R., Diibel, S. (eds) Antibody Engineering. Springer Protocols Handbooks. Springer, Berlin, Heidelberg; and Martin, ACR, Antibody Information: How to identify the CDRs by looking at a sequence [online] bioinf.org.uk/abs/info.html, all of which are incorporated by reference in their entireties. Various prediction algorithm tools are available and known for numbering antibody residues and CDRs (e.g., AbYsis, Abnum, AbYmod, AbRSA, IgBLAST, IMGT, or ANARCI).

[0075] The anti-SLC34A2 antibodies light chain and the heavy chain variable domains also contain the more highly conserved portions of variable domains called the framework regions (FR). The variable domains of native heavy and light chains each include four FR regions, largely by adopting a P-sheet configuration, connected by three CDRs, which form loops connecting, and in some cases forming part of, the P-sheet structure. The CDRs in each chain are held together in close proximity by the FR regions and, with the CDRs from the other chain, contribute to the formation of the target binding site of antibodies. See Kabat et al., Sequences of Proteins of Immunological Interest (National Institute of Health, Bethesda, Md. 1987), which can be used to identify and number CDR sequences within a variable domain.

[0076] The boundaries of a given CDR or FR may vary depending on the scheme used for identification. For example, the Kabat scheme is based on structural alignments, while the Chothia scheme is based on structural information. Numbering for both the Kabat and Chothia schemes is based upon the most common antibody region sequence lengths, in some cases with insertions. Insertions in the sequence relative to the standard numbering scheme are indicated using insertion letter codes. For example, residues that are inserted between residues L30 and L31 are indicated as L31A, L31B, etc. Deletions in the sequence relative to the standard scheme are accommodated by skipping numbers. The two schemes place certain insertions and deletions (“indels”) at different positions, resulting in differential numbering. For instance, the Chothia numbering scheme is nearly identical to the Kabat numbering scheme, except that insertions are placed at structural positions and topologically equivalents residues do get assigned the same numbers. The Contact scheme is based on analysis of complex crystal structures and is similar in many respects to the Chothia numbering scheme. The AbM scheme is a compromise between Kabat and Chothia definitions based on that used by Oxford Molecular’ s AbM antibody modeling software. The IgBLAST scheme is based on matching to germline V, D and J genes, and can be determined using National Center for Biotechnology Information (NCBI)’s IgBLAST tool.

[0077] In some embodiments, Kabat numbering can be determined by known sequence rules as described in, for example, Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. In some embodiments, the Kabat numbering scheme in some aspects can include any of the following rules to designate CDRs: CDR-L1 starts at approximately residue 24 of the light chain, always has a preceding C residue, and always has a following W residue; the end of CDR-L1 is defined by a stretch of 3 residues, where the W residue can be followed by Y, L, or F, followed by Q or L; CDR-1 has a length of 10 to 17 residues; CDR-L2 always starts 16 residues after the end of CDR-L1; the two residues before CDR-L2 are I and Y but can also be V and Y, I and K, or I and F; CDR-E2 is always 7 residues long; CDR-E3 always starts 33 residues after the end of CDR- E2, always has a preceding C residue, and is strictly followed by a F-G-X-G sequence motif, where X is any amino acid; CDR-E3 has a length of 7 to 11 residues; CDR-H1 starts at approximately position 26 of the heavy chain; the first amino acid in CDR-H1 is always 9 residues after a conserved C residue; CDR-H1 is followed by an invariant W residue followed by typically V, but also can be I or A; CDR-H1 has a length of 5 to 7 residues; CDR-H2 always starts at 15 residues after the end of CDR-H1; the first residue in CDR-H2 is usually preceded by the sequence motif E-E-W-I-G but a number of variations exist; the end of CDR-H2 is defined by a motif of 3 residues - the first residue of the motif of 3 residues can be either K or R, the second residue of the motif of 3 residues can be E, I, V, F, T, or A, the third residue of the motif of 3 residues can be T, S, I, or A; CDR-H2 has a length of 16 to 19 residues; CDR-H3 always starts 33 residues after the end of CDR-H2 and is always 3 residues after a C residue - the first residue of CDR-H3 is preceded by the conserved C residue followed by two residues, which are usually A- R; the residues following CDR-H3 is strictly followed by a W-G-X-G sequence motif, where the X is any amino acid; CDR-H3 typically has a length of 3 to 25 residues; CDR-H3 can be much longer than 25 residues. [0078] In some cases, according to the Chothia numbering scheme, exact boundary positions of certain CDRs can differ based on different definitions for the CDRs (See e.g., Martin, ACR, Antibody Information: How to identify the CDRs by looking at a sequence [online] bioinf.org.uk/abs/info.html). For example, in some instances, the boundary positions for CDR-L1 according to Chothia numbering can be L26— L32 (Chothia et al., Science, 1986; 233(4765):755- 8 and Chothia C. and Lesk A.M. J Mol Biol, 1987; 196(4):901-17). In some instances, the boundary positions for CDR-L1 can be L25— L32 (Al-Lazikani et al., J Mol Biol, 1997; 273(4):927-48). In some instances, the boundary positions for CDR-L2 can be L50— L52 and for CDR-L3 can be L91— L96 (Chothia et al., Science, 1986; 233(4765):755-8; Chothia C. and Lesk A.M. J Mol Biol, 1987; 196(4):901-17; and Al-Lazikani et al., J Mol Biol, 1997; 273(4):927-48). In some instances, the boundary positions for CDR-H1 according to Chothia numbering can be H26— H32 (Chothia et al., Science, 1986; 233(4765):755-8; Chothia C. and Lesk A.M. J Mol Biol, 1987; 196(4):901-17; and Al-Lazikani et al., J Mol Biol, 1997; 273(4):927-48). In some instances, the boundary positions for CDR-H2 can be H53— H55 (Chothia et al., Science, 1986; 233(4765):755-8 and Chothia C. and Lesk A.M. J Mol Biol, 1987, 196(4):901-17); H52a-H55 (Tramontane et al., J Mol Biol, 1990, 215(1): 175-82), or H52— H56 (Al-Lazikani et al., J Mol Biol., 1997; 273(4):927-48). In some instances, the boundary positions for CDR-H3 can be H96— H101 (Chothia et al., Science, 1986; 233(4765):755-8 and Chothia C. and Lesk A.M. J Mol Biol., 1987; 196(4):901-17). In some instances, the boundary positions for CDR-H3 can be H92— H104 (Morea et al., Biophys Chem, 1997; 68(1-3): 9-16 and Morea et al., J Mol Biol., 1998; 275(2): 269-94).

[0079] Table 2, below, exemplifies exemplary numbering and lists exemplary position boundaries of CDR-L1, CDR-L2, CDR-L3 and CDR-H1, CDR-H2, CDR-H3 as identified by Kabat, Chothia, AbM, and Contact schemes, respectively. For CDR-H1, residue numbering is listed using both the Kabat and Chothia numbering schemes. FRs are located between CDRs, for example, with FR-L1 located before CDR-L1, FR-L2 located between CDR-L1 and CDR-L2, FR-L3 located between CDR-L2 and CDR-L3 and so forth. It is noted that because the shown Kabat numbering scheme places insertions at H35A and H35B, the end of the Chothia CDR-H1 loop when numbered using the shown Kabat numbering convention varies between H32 and H34, depending on the length of the loop.

1 - Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD

2 - Al-Lazikani et al., J Mol Biol., 1997; 273(4):927-48).

[0080] Thus, unless otherwise specified, a “CDR” or “complementarity determining region,” or individual specified CDRs (e.g., CDR-H1, CDR-H2, CDR-H3), of a given antibody or region thereof, such as a variable region thereof, should be understood to encompass a (or the specific) complementarity determining region as defined by any of the aforementioned schemes, or other known schemes. For example, where it is stated that a particular CDR (e.g., a CDR-H3) contains the amino acid sequence of a corresponding CDR in a given VH or VL region amino acid sequence, it is understood that such a CDR has a sequence of the corresponding CDR (e.g., CDR- H3) within the variable region, as defined by any of the aforementioned schemes, or other known schemes. In some embodiments, where it is stated that an antibody or antigen-binding fragment thereof comprises a CDR-H1, a CDR-H2, and a CDR-H3 as contained within a given VH region amino acid sequence and a CDR-L1, a CDR-L2, and a CDR-L3 as contained within a given VL region amino acid sequence, the CDRs can be defined by any of the aforementioned schemes, such as Kabat, Chothia, AbM, IgBLAST, IMGT, or Contact method, or other known scheme. In some embodiments, specific CDR sequences are specified. Exemplary CDR sequences of provided antibodies are described using various numbering schemes, although it is understood that a provided antibody can include CDRs as described according to any of the other aforementioned numbering schemes or other known numbering schemes.

[0081] Likewise, unless otherwise specified, a FR or individual specified FR(s) (e.g., FR-H1, FR-H2, FR-H3, FR-H4, FR-L1, FR-L2, FR-L3, and/or FR-L4), of a given antibody or region thereof, such as a variable region thereof, should be understood to encompass a (or the specific) framework region as defined by any of the known schemes. In some instances, the scheme for identification of a particular CDR, FR, or FRs or CDRs is specified, such as the CDR as defined by the Kabat, Chothia, AbM, IgBLAST, IMGT, or Contact method, or other known schemes. In other cases, the particular amino acid sequence of a CDR or FR is given. In some embodiments, where it is stated that an antibody or antigen-binding fragment thereof comprises a FR-H1, a FR- H2, a FR-H3, and a FR-H4 as contained within a given VH region amino acid sequence and a FR- LI, a FR-L2, a FR-L3, and a FR-L4 as contained within a given VL region amino acid sequence, the FRs can be defined by any of the aforementioned schemes, such as Kabat, Chothia, AbM, IgBLAST, IMGT, or Contact method, or other known scheme.

[0082] In some embodiments, the anti-SLC34A2 antibody or antigen-binding fragment thereof contains a VH region and a VL region containing a combination of six CDRs as described herein. In some embodiments, the combination of six CDRs are those described in Tables provided in the Examples (e.g., Table El). In some embodiments, the anti-SLC34A2 antibody contains a VH region and a VL region as described. In any such embodiments, a VH region sequence can be any of the VH region sequence described herein. In any such embodiments, a VL region sequence can be any of the VL region sequence described herein. In any such embodiments, any of the VH region sequence and any of the VL region sequence described herein can be used in combination. In some such embodiments, the antibody is an antigen-binding fragment, such as a Fab or an scFv.

[0083] In some embodiments, the antibody or antigen-binding fragment further comprises at least a portion of an immunoglobulin constant region or a variant thereof. For instance, depending on the particular format of an antigen-binding fragment of an antibody, the portion of a light and heavy chain constant regions may be CL and CHI only, respectively, such as present in a Fab. In other examples, the heavy and light chain may be a longer portion such as a full length constant sequence including a CL of a light chain (e.g., human light chain) and a CHI, hinge, CH2 and CH3 sequence of a heavy chain (e.g., human heavy chain). In some embodiments, an anti- SLC34A2 antibody comprises at least one heavy chain comprising a VH region and at least a portion of a heavy chain constant region, and at least one light chain comprising a VL region and at least a portion of a light chain constant region. In some embodiments, an anti-SLC34A2 antibody comprises two heavy chains, wherein each heavy chain comprises a VH region and at least a portion of a heavy chain constant region, and two light chains, wherein each light chain comprises a VL region and at least a portion of a light chain constant region. In some such embodiments, the antibody is a full-length antibody that also contains a constant region, light chain and heavy chain constant regions. In some embodiments, an anti-SLC34A2 antibody comprises two heavy chains, wherein each heavy chain comprises a VH region and a heavy chain constant region, and two light chains, wherein each light chain comprises a VL region and a light chain constant region. In particular embodiments, the immunoglobulin constant regions are human constant regions. [0084] In some embodiments, a provided antibody is a humanized antibody, including a full length antibody or an antigen-binding fragment thereof. In some embodiments, the humanized antibody is a full length antibody that includes human immunoglobulin constant regions. In some embodiments, the humanized antibody is an antigen-binding fragment, such as Fv, scFv, Fab, Fab', F(ab')2 or other antigen-binding fragment of antibodies.

[0085] In some embodiments, a humanized antibody has one or more amino acid residues introduced into it from a source, which is non-human. These non-human amino acid residues are often referred to as "import" residues, which are typically taken from an "import" variable domain. Humanization may be essentially performed by substituting CDRs for the corresponding sequences of a human antibody. In some embodiments, a humanized antibody is a human antibody in which some CDRs and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies, such as murine antibodies. Accordingly, such humanized antibodies are chimeric wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In some embodiments, methods for humanizing a non-human antibody generally involve CDR-grafting to confer donor CDR binding affinity onto an antibody acceptor variable region framework. In some embodiments, CDR-grafting alone can lead to a significant reduction or complete loss of binding affinity, as a set of supporting framework residues can, in some cases, be important for maintaining the conformation of the CDRs. In some embodiments, modification such as by mutation in the FR can be carried out to improve binding affinity, including in some cases reintroducing murine residues into the human framework. Embodiments of a method also can involve optimizing the binding affinity of an antibody variable region.

[0086] In some embodiments, the sequence of the humanized antibody is one characterized as meeting requirements defined by The World Health Organization (WHO) International Nonproprietary Name (INN) Expert Group for non-human derived antibodies to be considered "humanized". According to guidelines, comparison of a candidate antibody to human sequences should be done through the International Immunogenetics Information System® (IMGT®) DomainGapAlign tool (www.imgt.org). This tool interrogates the IMGT® database of antibody germline variable region genes where the alignment score is made only against germline sequence variable region exons, thus omitting part of CDR3 and the J region from the analysis. For an antibody to be "humanized", in addition to being "closer to human than to other species", the top "hit" should be human and the identity to human sequences must be at least 85%, otherwise the antibody would be designated as "chimeric". For further details, see Jones et al., Nature, 321: 522-525, 1986; Reichmann et al., Nature, 332: 323-329, 1988; Presta, Curr. Op.

Struct. Biol., 2: 593-596, 1992.

[0087] In some embodiments, a humanized antibody can comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In some embodiments, these modifications are made to further refine and optimize antibody performance.

[0088] In some embodiments, provided antibodies and antigen-binding fragments have a sequence, including as a result of substitutions proposed during the humanization, that do not affect the affinity or stability of the antibody.

[0089] In some embodiments, provided anti-SLC34A2 antibodies, including antigen-binding fragments thereof, include any combination of the heavy chain and light chain complementaritydetermining regions (CDRs) described herein. In some embodiments, the anti-SLC34A2 antibody or antigen-binding fragment thereof comprises any one of the CDR-H1 as described herein, any one of the CDR-H2 as described herein, any one of the CDR-H3 as described herein, any one of the CDR-L1 as described herein, any one of the CDR-L2 as described herein and any one of the CDR-L3 as described herein. In some of any such embodiments, any one or more of the CDR- Hl, the CDR-H2 and the CDR-H3 sequences described herein, and any one or more of the CDR- Ll, the CDR-L2 and the CDR-L3 sequences described herein can be used in combination.

[0090] Also among the antibodies are those having sequences at least at or about 90%, at or about 91%, at or about 92%, at or about 93%, at or about 94%, at or about 95%, at or about 96%, at or about 97%, at or about 98%, or at or about 99% identical to any such CDR sequence, e.g., any of the CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, CDR-L3. In some embodiments, among the antibodies are those in which a CDR contained therein has no more than 2 amino acid difference compared to any such above CDR sequence, e.g., any of the CDR-H1, CDR-H2, CDR- H3, CDR-L1, CDR-L2, CDR-L3. In some embodiments, among the antibodies are those in which a CDR contained therein has no more than 1 amino acid difference compared to any such above CDR sequence, e.g., any of the CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, CDR-L3.

[0091] In some embodiments, a provided anti-SLC34A2 antibody or an antigen-binding fragment thereof has a CDR-H1, a CDR-H2 and a CDR-H3 present in a VH region amino acid sequence set forth in any one of SEQ ID NOs: 1, 9, 15, 23, 31, 39, 47, 53, 59, 66, 73, 78, 84, 90, 94, 100, 161, 163, 165, 166, 168, 169, 170, 172, 174, 175, 176, 178, 180, 182, 184 and 185 or an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the VH region amino acid sequence set forth in any one of SEQ ID NOs: 1, 9, 15, 23, 31, 39, 47, 53, 59, 66, 73, 78, 84, 90, 94, 100, 161, 163, 165, 166, 168, 169, 170, 172, 174, 175, 176, 178, 180, 182, 184 and 185 and a CDR-L1, a CDR-L2 and a CDR-L3 present in a VL region amino acid sequence set forth in any one of SEQ ID NOs: 5, 13, 19, 27, 35, 43, 51, 56, 63, 70, 76, 82, 88, 93, 97, 103, 154, 155, 156,

157, 158, 159, 160, 162, 164, 167, 171, 173, 177, 179, 181 and 183 or an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the VL region amino acid sequence set forth in any one of SEQ ID NOs: 5, 13, 19, 27, 35, 43, 51, 56, 63, 70, 76, 82, 88, 93, 97, 103, 154, 155, 156, 157,

158, 159, 160, 162, 164, 167, 171, 173, 177, 179, 181 and 183. In some embodiments, a provided anti-SLC34A2 antibody or an antigen-binding fragment thereof has a CDR-H1, a CDR-H2 and a CDR-H3 present in a VH region amino acid sequence set forth in any one of SEQ ID NOs: 1, 9, 15, 23, 31, 39, 47, 53, 59, 66, 73, 78, 84, 90, 94, 100, 161, 163, 165, 166, 168, 169, 170, 172, 174, 175, 176, 178, 180, 182, 184 and 185, and a CDR-L1, a CDR-L2 and a CDR-L3 present in a VL region amino acid sequence set forth in any one of SEQ ID NOs: 5, 13, 19, 27, 35, 43, 51, 56, 63, 70, 76, 82, 88, 93, 97, 103, 154, 155, 156, 157, 158, 159, 160, 162, 164, 167, 171, 173, 177, 179, 181 and 183. In some embodiments, the combination of six CDRs (a CDR-H1, a CDR-H2, a CDR-H3, a CDR-L1, a CDR-L2 and a CDR-L3) is according to Kabat numbering.

[0092] Exemplary heavy and light chain CDR sequences of the anti-SLC34A2 antibodies or antigen-binding fragments thereof are provided in the Sequence Table provided herein.

[0093] In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 2, a CDR-H2 set forth in SEQ ID NO: 3, and a CDR-H3 set forth in SEQ ID NO: 4; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 6, a CDR-L2 set forth in SEQ ID NO: 7, and a CDR-L3 set forth in SEQ ID NO: 8. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 10, a CDR-H2 set forth in SEQ ID NO: 11, and a CDR-H3 set forth in SEQ ID NO: 12; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 6, a CDR-L2 set forth in SEQ ID NO: 7, and a CDR-L3 set forth in SEQ ID NO: 14. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 16, a CDR-H2 set forth in SEQ ID NO: 17, and a CDR-H3 set forth in SEQ ID NO: 18; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 20, a CDR-L2 set forth in SEQ ID NO: 21, and a CDR-L3 set forth in SEQ ID NO: 22. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 24, a CDR-H2 set forth in SEQ ID NO: 25, and a CDR-H3 set forth in SEQ ID NO: 26; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 28, a CDR-L2 set forth in SEQ ID NO: 29, and a CDR-L3 set forth in SEQ ID NO: 30. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 32, a CDR-H2 set forth in SEQ ID NO: 33, and a CDR-H3 set forth in SEQ ID NO: 34; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 36, a CDR-L2 set forth in SEQ ID NO: 37, and a CDR-L3 set forth in SEQ ID NO: 38. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 40, a CDR-H2 set forth in SEQ ID NO: 41, and a CDR-H3 set forth in SEQ ID NO: 42; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 44, a CDR-L2 set forth in SEQ ID NO: 45, and a CDR-L3 set forth in SEQ ID NO: 46. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 48, a CDR-H2 set forth in SEQ ID NO: 49, and a CDR-H3 set forth in SEQ ID NO: 50; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 36, a CDR-L2 set forth in SEQ ID NO: 21, and a CDR-L3 set forth in SEQ ID NO: 52. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 48, a CDR-H2 set forth in SEQ ID NO: 54, and a CDR-H3 set forth in SEQ ID NO: 55; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 36, a CDR-L2 set forth in SEQ ID NO: 57, and a CDR-L3 set forth in SEQ ID NO: 58. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 60, a CDR-H2 set forth in SEQ ID NO: 61, and a CDR-H3 set forth in SEQ ID NO: 62; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 64, a CDR-L2 set forth in SEQ ID NO: 21, and a CDR-L3 set forth in SEQ ID NO: 65. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 67, a CDR-H2 set forth in SEQ ID NO: 68, and a CDR-H3 set forth in SEQ ID NO: 69; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 64, a CDR-L2 set forth in SEQ ID NO: 21, and a CDR-L3 set forth in SEQ ID NO: 65. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 67, a CDR-H2 set forth in SEQ ID NO: 68, and a CDR-H3 set forth in SEQ ID NO: 69; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 28, a CDR-L2 set forth in SEQ ID NO: 71, and a CDR-L3 set forth in SEQ ID NO: 72. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 32, a CDR-H2 set forth in SEQ ID NO: 74, and a CDR-H3 set forth in SEQ ID NO: 75; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 36, a CDR-L2 set forth in SEQ ID NO: 21, and a CDR-L3 set forth in SEQ ID NO: 77. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 79, a CDR-H2 set forth in SEQ ID NO: 80, and a CDR-H3 set forth in SEQ ID NO: 81; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 36, a CDR-L2 set forth in SEQ ID NO: 21, and a CDR-L3 set forth in SEQ ID NO: 83. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 85, a CDR-H2 set forth in SEQ ID NO: 86, and a CDR-H3 set forth in SEQ ID NO: 87; and the V_L region contains a CDR-L1 set forth in SEQ ID NO: 89, a CDR-L2 set forth in SEQ ID NO: 21, and a CDR-L3 set forth in SEQ ID NO: 65. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 10, a CDR-H2 set forth in SEQ ID NO: 91, and a CDR-H3 set forth in SEQ ID NO: 92; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 6, a CDR-L2 set forth in SEQ ID NO: 7, and a CDR-L3 set forth in SEQ ID NO: 8. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 95, a CDR-H2 set forth in SEQ ID NO: 3, and a CDR-H3 set forth in SEQ ID NO: 96; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 36, a CDR-L2 set forth in SEQ ID NO: 98, and a CDR-L3 set forth in SEQ ID NO: 99. In some of any of the provided embodiments, the VH region contains a CDR-H1 set forth in SEQ ID NO: 101, a CDR-H2 set forth in SEQ ID NO: 102, and a CDR-H3 set forth in SEQ ID NO: 96; and the VL region contains a CDR-L1 set forth in SEQ ID NO: 36, a CDR-L2 set forth in SEQ ID NO: 104, and a CDR-L3 set forth in SEQ ID NO: 105.

[0094] In some embodiments, a provided VH sequence comprises an N-terminal amino acid residue that is a glutamine (Q) or a pyroglutamate (pE). Recombinant monoclonal antibodies can undergo spontaneous or non- spontaneous (e.g., enzymatically catalyzed by glutaminyl cyclase) cyclization of Q at the N-terminus, resulting in pE (Liu et al. J Bio; Chem, volume 286:13 (2011)). In some embodiments, the VH can be a sequence set forth in any one of SEQ ID NOS: 1, 9, 15, 23, 31, 39, 47, 53, 59, 66, 73, 78, 84, 90, 94, 100, 161, 163, 165, 166, 168, 169, 170, 172, 174, 175, 176, 178, 180, 182, 184, and 185. In some embodiments, the VH can be any of the sequences set forth in Table 3, wherein X is Q or pE.

[0095] In some embodiments, a provided VL sequence comprises an N-terminal amino acid residue that is a glutamic acid (E) or a pyroglutamate (pE). Recombinant monoclonal antibodies can undergo spontaneous or non- spontaneous (e.g., enzymatically catalyzed by glutaminyl cyclase) cyclization of E at the N-terminus, resulting in pE (Liu et al. J Bio; Chem, volume 286:13 (2011)). In some embodiments, the VL can be a sequence set forth in any one of SEQ ID NOS: 5, 162, 13, 164, 27, 167, 51, 171, 56, 173, 76, 177, 82, 179, 88, 181, 93 and 183. In some embodiments, the VL can be any of the sequences set forth in Table 4, wherein X is E or pE.

[0096] In some embodiments, a provided VL sequence comprises N-terminal amino acid residues DIQ. In some embodiments, the first N-terminal amino acid residue, the second N- terminal amino acid residue, and the third N-terminal amino acid residue is D, I, and Q, respectively. In some embodiments, the VL can be a sequence set forth in any of SEQ ID NOS: 154 to 160. In some embodiments, a provided VL sequence comprises N-terminal amino acid residues AIR. In some embodiments, the first N-terminal amino acid residue, the second N- terminal amino acid residue, and the third N-terminal amino acid residue is A, I, and R, respectively. In some embodiments, the VL can be a sequence set forth in any of SEQ ID NOS: 19, 35, 43, 63, 70, 97, and 103. In some embodiments, the VL can be any of the sequences set forth in Table 5.

[0097] In some embodiments, any of the provided anti-SLC34A2 antibodies or antigen binding fragments has a VH region having the amino acid sequence set forth in any one of SEQ ID Nos: 1, 9, 15, 23, 31, 39, 47, 53, 59, 66, 73, 78, 84, 90, 94, 100, 161, 163, 165, 166, 168, 169, 170, 172, 174, 175, 176, 178, 180, 182, 184 and 185, or an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the VH region amino acid sequence set forth in any one of SEQ ID Nos: 1, 9, 15, 23, 31, 39, 47, 53, 59, 66, 73, 78, 84, 90, 94, 100, 161, 163, 165, 166, 168, 169, 170, 172, 174, 175, 176, 178, 180, 182, 184 and 185, and has a VL region having the amino acid sequence set forth in any one of SEQ ID Nos: 5, 13, 19, 27, 35, 43, 51, 56, 63, 70, 76, 82, 88, 93, 97, 103,

154, 155, 156, 157, 158, 159, 160, 162, 164, 167, 171, 173, 177, 179, 181 and 183, or an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the VL region amino acid sequence set forth in any one of SEQ ID NOs: 5, 13, 19, 27, 35, 43, 51, 56, 63, 70, 76, 82, 88, 93, 97, 103, 154,

155, 156, 157, 158, 159, 160, 162, 164, 167, 171, 173, 177, 179, 181 and 183.

[0098] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 1 or SEQ ID NO: 161, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 5 or SEQ ID NO: 162. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 1, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 5. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 161, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 162. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 1, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 162. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 161, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 5.

[0099] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 9 or SEQ ID NO: 163, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 13 or SEQ ID NO: 164. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 9, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 13. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 163, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 164. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 9, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 164. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 163, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 13.

[0100] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 15 or SEQ ID NO: 165, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 19 or SEQ ID NO: 154. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 15, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 19. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 165, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 154. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 15, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 154. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 165, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 19.

[0101] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 23 or SEQ ID NO: 166, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 27 or SEQ ID NO: 167. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 23, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 27. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 166, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 167. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 23, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 167. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 166, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 27.

[0102] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 31 or SEQ ID NO: 168, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 35 or SEQ ID NO: 155. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 31, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 35. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 168, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 155. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 31, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 155. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 168, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 35.

[0103] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 39 or SEQ ID NO: 169, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 43 or SEQ ID NO: 156. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 39, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 43. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 169, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 156. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 39, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 156. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 169, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 43.

[0104] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 47 or SEQ ID NO: 170, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 51 or SEQ ID NO: 171. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 47, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 51. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 170, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 171. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 47, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 171. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 170, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 51.

[0105] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 53 or SEQ ID NO: 172, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 56 or SEQ ID NO: 173. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 53, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 56. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 172, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 173. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 53, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 173. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 172, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 56.

[0106] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 59 or SEQ ID NO: 174, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 63 or SEQ ID NO: 157. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 59, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 63. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 174, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 157. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 59, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 157. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 174, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 63.

[0107] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 66 or SEQ ID NO: 175, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 70 or SEQ ID NO: 158. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 66, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 70. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 175, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 158. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 66, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 158. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 175, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 70.

[0108] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 73 or SEQ ID NO: 176, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 76 or SEQ ID NO: 177. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 73, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 76. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 176, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 177. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 73, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 177. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 176, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 76.

[0109] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 78 or SEQ ID NO: 178, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 82 or SEQ ID NO: 179. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 78, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 82. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 178, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 179. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 78, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 179. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 178, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 82.

[0110] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 84 or SEQ ID NO: 180, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 88 or SEQ ID NO: 181. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 84, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 88. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 180, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 181. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 84, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 181. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 180, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 88.

[0111] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 90 or SEQ ID NO: 182, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 93 or SEQ ID NO: 183. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 90, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 93. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 182, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 183. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 90, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 183. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 182, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 93.

[0112] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 94 or SEQ ID NO: 184, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 97 or SEQ ID NO: 159. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 94, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 97. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 184, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 159. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 94, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 159. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 184, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 97.

[0113] In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 100 or SEQ ID NO: 185, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 103 or SEQ ID NO: 160. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 100, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 103. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 185, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 160. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 100, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 160. In some embodiments, the VH region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 185, and the VL region is or comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 103.

[0114] In some embodiments, the VH region of the antibody or antigen-binding fragment thereof comprises the amino acid sequence of any one of SEQ ID NOs: 1, 9, 15, 23, 31, 39, 47, 53, 59, 66, 73, 78, 84, 90, 94, 100, 161, 163, 165, 166, 168, 169, 170, 172, 174, 175, 176, 178, 180, 182, 184 and 185 and the VL region of the antibody or antigen-binding fragment comprises the amino acid sequence of any one of SEQ ID NOs: 5, 13, 19, 27, 35, 43, 51, 56, 63, 70, 76, 82, 88, 93, 97, 103,154, 155, 156, 157, 158, 159, 160, 162, 164, 167, 171, 173, 177, 179, 181 and 183.

[0115] In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 1 or SEQ ID NO: 161 and SEQ ID NO: 5 or SEQ ID NO: 162, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 9 or SEQ ID NO: 163 and SEQ ID NO: 13 or SEQ ID NO: 164, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 15 or SEQ ID NO: 165 and SEQ ID NO: 19 or SEQ ID NO: 154, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 23 or SEQ ID NO: 166 and SEQ ID NO: 27 or SEQ ID NO: 167, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 31 or SEQ ID NO: 168 and SEQ ID NO: 35 or SEQ ID NO: 155, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 39 or SEQ ID NO: 169 and SEQ ID NO: 43 or SEQ ID NO: 156, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 47 or SEQ ID NO: 170 and SEQ ID NO: 51 or SEQ ID NO: 171, respectively. In some embodiments of the antibody or antigenbinding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 53 or SEQ ID NO: 172 and SEQ ID NO: 56 or SEQ ID NO: 173, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 59 or SEQ ID NO: 174 and SEQ ID NO: 63 or SEQ ID NO: 157, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 66 or SEQ ID NO: 175 and SEQ ID NO: 70 or SEQ ID NO: 158, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 73 or SEQ ID NO: 176 and SEQ ID NO: 76 or SEQ ID NO: 177, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 78 or SEQ ID NO: 178 and SEQ ID NO: 82 or SEQ ID NO: 179, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 84 or SEQ ID NO: 180 and SEQ ID NO: 88 or SEQ ID NO: 181, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 90 or SEQ ID NO: 182 and SEQ ID NO: 93 or SEQ ID NO: 183, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 94 or SEQ ID NO: 184 and SEQ ID NO: 97 or SEQ ID NO: 159, respectively. In some embodiments of the antibody or antigenbinding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 100 or SEQ ID NO: 185 and SEQ ID NO: 103 or SEQ ID NO: 160, respectively.

[0116] In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 1 and 5, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 9 and 13, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 15 and 19, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 23 and 27, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 31 and 35, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 39 and 43, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 47 and 51, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 53 and 56, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 59 and 63, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 66 and 70, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 73 and 76, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 78 and 82, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 84 and 88, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 90 and 93, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 94 and 97, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 100 and 103, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 15 and 154, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 31 and 155, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 39 and 156, respectively. In some embodiments of the antibody or antigenbinding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 59 and 157, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 66 and 158, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 94 and 159 respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 100 and 160, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 161 and 162, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 1 and 162, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 161 and 5, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 163 and 164, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 9 and 164, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 163 and 13, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 165 and 154, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 165 and 19, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 166 and 167, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 166 and 27, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 23 and 167, respectively. In some embodiments of the antibody or antigenbinding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 168 and 155, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 168 and 35, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 169 and 156, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 169 and 43, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 170 and 171, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 47 and 171, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 170 and 51, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 172 and 173, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 53 and 173, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 172 and 56, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 174 and 157, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 174 and 63, respectively. In some embodiments of the antibody or antigenbinding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 175 and 158, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 175 and 70, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 176 and 177, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 73 and 177, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 176 and 76, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 178 and 179, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 78 and 179, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 178 and 82, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 180 and 181, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 84 and 181, respectively. In some embodiments of the antibody or antigenbinding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 180 and 88, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 182 and 183, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 90 and 183, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 182 and 93, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 184 and 159, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 184 and 97, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 185 and 160, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 185 and 103, respectively.

[0117] Among the provided antibodies are antibody fragments. An “antibody fragment” or “antigen-binding fragment” refers to a molecule other than an intact antibody that comprises a portion of an intact antibody that binds the antigen to which the intact antibody binds. Typically, an antigen binding fragment includes all CDRs of a variable heavy chain (VH) and variable light chain (VL) sequence from antibodies that bind SLC34A2 set forth herein. Examples of antibody fragments include but are not limited to Fv, Fab, Fab’, Fab’-SH, F(ab’)2; diabodies; linear antibodies; and heavy chain variable (VH) regions, single-chain antibody molecules such as scFvs and single-domain antibodies comprising only the VH region. Papain digestion of antibodies produce two identical antigen-binding fragments, called “Fab” fragments, and a residual “Fc” fragment, a designation reflecting the ability to crystallize readily. The Fab fragment is composed of an entire L chain along with the variable region domain of the H chain (VH), and the first constant domain of one heavy chain (CHI). Each Fab fragment is monovalent with respect to antigen binding, i.e., it has a single antigen-binding site. Pepsin treatment of an antibody yields a single large F(ab’)2 fragment which roughly corresponds to two disulfide linked Fab fragments having different antigen-binding activity and is still capable of cross-linking antigen. Fab’ fragments differ from Fab fragments by having a few additional residues at the carboxy terminus of the CHI domain including one or more cysteines from the antibody hinge region. Fab’-SH is the designation herein for Fab’ in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab’)2 antibody fragments originally were produced as pairs of Fab’ fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known. In some embodiments, the antibody is or comprises an antibody fragment comprising a variable heavy chain (VH) and a variable light chain (VL) region. In particular embodiments, the antibodies are single-chain antibody fragments comprising a heavy chain variable (VH) region and/or a light chain variable (VL) region, such as scFvs.

[0118] Antigen-binding fragments can be made by various techniques, including but not limited to proteolytic digestion of an intact antibody as well as production by recombinant host cells. In some embodiments, the antibodies are recombinantly -produced fragments, such as fragments comprising arrangements that do not occur naturally, such as those with two or more antibody regions or chains joined by synthetic linkers, e.g., peptide linkers, and/or that may not be produced by enzyme digestion of a naturally-occurring intact antibody. In some aspects, the antibody fragments are scFvs.

[0119] The term “F(ab)” refers to two of the protein fragments resulting from proteolytic cleavage of immunoglobulin G (IgG) molecules by the enzyme papain. Each F(ab) comprises a covalent heterodimer of the VH chain and VL chain and includes an intact antigen-binding site.

[0120] The term “F(ab)2” refers to a protein fragment of IgG generated by proteolytic cleavage by the enzyme pepsin. Each F(ab’)2 fragment comprises two F(ab) fragments, thus comprising both antigen-binding sites.

[0121] An “Fv fragment” for use according to certain embodiments of the present invention can be produced by preferential proteolytic cleavage of an IgM, and on rare occasions of an IgG or IgA immunoglobulin molecule. Fv fragments are, however, more commonly derived using recombinant techniques known in the art. The Fv fragment includes a non-covalent VH"VL heterodimer including an antigen-binding site which retains much of the antigen recognition and binding capabilities of the native antibody molecule, but lacking the CHI and CL domains contained within a Fab. Inbar et al. (1972) Proc. Nat. Acad. Sci. USA 69:2659-2662; Hochman et al. (1976) Biochem 15:2206-2210; and Ehrlich et al. (1980) Biochem 79:4091-4096. [0122] In certain embodiments, single chain Fv (scFv) antibodies are contemplated and may be prepared using standard molecular biology techniques following the teachings of the present application with regard to selecting antibodies having the desired specificity. In some embodiments, the antibody or antigen-binding fragment thereof is a single-chain antibody fragment, such as a single chain variable fragment (scFv). In some embodiments, the antibody or antigen binding fragment is a multi-domain antibody, such as an scFv comprising a heavy chain variable (VH) region and a light chain variable (VL) region. In some embodiments, the singlechain antibody fragment (e.g., scFv) includes one or more linkers joining two antibody domains or regions, such as a heavy chain variable (VH) region and a light chain variable (VL) region. The linker typically is a peptide linker, e.g., a flexible and/or soluble peptide linker. Among the linkers are those rich in glycine and serine and/or in some cases threonine. In some embodiments, the linkers further include charged residues such as lysine and/or glutamate, which can improve solubility. In some embodiments, the linkers further include one or more proline.

[0123] In some embodiments, the VH and VL of the scFv can be arranged or linked to each other in any orientation. In some embodiments, the VH of the scFv can be amino-terminal to the VL of the scFv. In some embodiments, the VL of the scFv can be amino-terminal to the VH of the scFv. In some embodiments, the VH of the scFv is amino-terminal to the VL of the scFv. In some embodiments, the VL of the scFv is amino-terminal to the VH of the scFv.

[0124] In some aspects, the linkers rich in glycine and serine (and/or threonine) include at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% such amino acid(s). In some embodiments, they include at least at or about 50%, 55%, 60%, 70%, or 75%, glycine, serine, and/or threonine. In some embodiments, the linker is comprised substantially entirely of glycine, serine, and/or threonine. The linkers generally are between about 5 and about 50 amino acids in length, typically between at or about 10 and at or about 30, e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30, and in some examples between 10 and 25 amino acids in length. Exemplary linkers include linkers having various numbers of repeats of the sequence GGGGS (4GS; SEQ ID NO: 116) or GGGS (3GS; SEQ ID NO: 117), such as between 2, 3, 4 and 5 repeats of such a sequence. Exemplary linkers include those having or consisting of a sequence set forth in SEQ ID NO: 118 (GGGGSGGGGSGGGGS). Exemplary linkers further include those having or consisting of the sequence set forth in SEQ ID NO: 119 (GSTSGSGKPGSGEGSTKG). Exemplary linkers further include those having or consisting of the sequence set forth in SEQ ID NO: 120 (SRGGGGSGGGGSGGGGSLEMA). An exemplary linker includes those having or consisting of the sequence set forth in SEQ ID NO: 121 (GSRGGGGSGGGGSGGGGSLEMA) .

[0125] In still further embodiments, chimeric antibodies may be made. For example, a chimeric antibody may comprise CDRs and framework regions from different antibodies. These antibodies may be produced through recombinant molecular biological techniques or may be physically conjugated together.

[0126] A scFv polypeptide is a covalently linked VH"VL heterodimer which is expressed from a gene fusion including Vn- and Vi.-cncoding genes linked by a peptide-encoding linker. Huston et al. (1988) Proc. Nat. Acad. Sci. USA S5(16):5879-5883. A number of methods have been described to discern chemical structures for converting the naturally aggregated — but chemically separated — light and heavy polypeptide chains from an antibody V region into an scFv molecule which will fold into a three dimensional structure substantially similar to the structure of an antigen-binding site. See, e.g., U.S. Pat. Nos. 5,091,513 and 5,132,405, to Huston et al. and U.S. Pat. No. 4,946,778, to Ladner et al.

[0127] In certain embodiments, the antibodies of the present disclosure may be chimeric antibodies. In this regard, a chimeric antibody is comprised of an antigen-binding fragment of an anti-SLC34A2 antibody operably linked or otherwise fused to a heterologous Fc portion of a different antibody. In certain embodiments, the heterologous Fc domain is of human origin. In further embodiments, the heterologous Fc domain may be from a different Ig class from the parent antibody, including IgA (including subclasses IgAl and IgA2), IgD, IgE, IgG (including subclasses IgGl, IgG2, IgG3, and IgG4), and IgM. In further embodiments, the heterologous Fc domain may be comprised of CH2 and CH3 domains from one or more of the different Ig classes. In some embodiments, the heterologous Fc domain is of non-human origin. In some embodiments, the Fc domain is of murine origin. In some embodiments, the Fc domain has an amino acid sequence that is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the sequence set forth in SEQ ID NO: 110. In some embodiments, the Fc domain comprises the amino acid sequence set forth in SEQ ID NO: 110.

[0128] In certain embodiments, the antibodies of the present disclosure may be “non- naturally occurring” antibodies. Non-naturally occurring antibodies can refer to antibodies that comprise one or more amino acid modifications, such that the resultant antibody is substantially non-naturally occurring e.g., does not exists in nature). These amino acid modifications can include point mutations, wherein a naturally occurring amino acid is substituted for another naturally occurring amino acid. In some embodiments, the amino acid modifications can include point mutations wherein a non-naturally occurring amino acid is substituted for a naturally occurring amino acid. Non-naturally occurring antibodies can also refer to antibodies that are conjugated to a heterologous protein or compound, such as a detectable marker.

[0129] Table El provides the SEQ ID NOS: of exemplary provided antibody or antigenbinding fragment thereof. In some embodiments, the SLC34A2-binding antibody or fragment thereof comprises a VH region that comprises the CDR-H1, the CDR-H2 and the CDR-H3 sequence and a VL region that comprises the CDR-L1, the CDR-L2 and the CDR-L3 sequence set forth in the SEQ ID NOS: listed in each row of Table El in Example 1 (by Kabat numbering scheme). In some embodiments, the SLC334A2-binding antibody or fragment thereof comprises a VH region sequence and a VL region sequence set forth in the SEQ ID NOS: listed in each row of Table El, or an antibody comprising a VH region and a VL region amino acid sequence that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the VH region sequence and the VL region sequence set forth in the SEQ ID NOS: listed in each row of Table El. In some embodiments, the SLC34A2-binding antibody or fragment thereof comprises a VH region sequence and a VL region sequence set forth in the SEQ ID NOS: listed in each row of Table El.

[0130] In some embodiments, the provided antibody or antigen-binding fragment thereof comprises a VH region and a VL region, wherein the VH region of the antibody or antigen-binding fragment thereof can contain a combination of any of the CDR-H1, the CDR-H2 and the CDR- H3 amino acid sequences set forth in Table El, and the VL region of the antibody or antigenbinding fragment thereof can contain a combination of any of the CDR-L1, the CDR-L2 and the CDR-L3 amino acid sequences set forth in Table El. In some embodiments, the provided antibody or antigen-binding fragment thereof comprises a VH region and/or a VL region set forth in Table El, in any combination, orientation or containing a different linker. In some aspects, the antibody or antigen-binding fragment thereof comprises a VH region described in Table El. In some aspects, the antibody or antigen-binding fragment thereof comprises a VL region described in Table El.

[0131] In some embodiments, the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR- H2), and a heavy chain complementarity determining region 3 (CDR-H3) comprising the sequences set forth in SEQ ID NOS: 2, 3, and 4, respectively, and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR- L3) comprising the sequences set forth in SEQ ID NOS: 6, 7, and 8, respectively. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 1 and 5 respectively. In some embodiments, the sequence of the VH is a sequence in which the first N-terminal Q SEQ ID NO: 1 is a pyroglutamate. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region is or comprises the sequence set forth in SEQ ID NO: 1 in which the first N-terminal Q of SEQ ID NO: 1 is a pyroglutamate and the VL region is or comprises the sequence set forth in SEQ ID NO:5. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 162 and 5 respectively.

[0132] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2 and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 11 and 12, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7, and 14, respectively. In some embodiments of the antibody or antigenbinding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 9 and 13, respectively. In some embodiments, the sequence of the VH is a sequence in which the first N-terminal Q SEQ ID NO: 9 is a pyroglutamate. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region is or comprises the sequence set forth in SEQ ID NO: 9 in which the first N-terminal Q of SEQ ID NO: 9 is a pyroglutamate and the VL region is or comprises the sequence set forth in SEQ ID NO: 13. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 164 and 13, respectively.

[0133] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2 and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 16, 17 and 18, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 20, 21 and 22, respectively. In some embodiments of the antibody or antigenbinding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 15 and 19. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region and the VL region are or comprise the sequence set forth in SEQ ID NO: 15 and 154. In some embodiments, the sequence of the VH is a sequence in which the first N-terminal Q SEQ ID NO: 15 is a pyroglutamate. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region is or comprises the sequence set forth in SEQ ID NO: 15 in which the first N-terminal Q of SEQ ID NO: 15 is a pyroglutamate and the VL region is or comprises the sequence set forth in SEQ ID NO: 19. In some embodiments of the antibody or antigen-binding fragment provided herein, the VH region is or comprises the sequence set forth in SEQ ID NO: 15 in which the first N-terminal Q of SEQ ID NO: 15 is a pyroglutamate and the VL region is or comprises the sequence set forth in SEQ ID NO: 154.

[0134] In certain embodiments, antibody variable domains as described are fused to immunoglobulin constant domain sequences. In certain embodiments, the fusion is with an Ig heavy chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. In some of any of the embodiments herein, the antibody further comprises a heavy chain constant domain and/or a light chain constant domain. In some embodiments, the heavy chain and/or light constant domain is murine or human.

[0135] A “constant region” or “constant domain” is a domain in an antibody heavy or light chain that contains a sequence of amino acids that is comparatively more conserved among antibodies than the variable region domain. The constant regions of immunoglobulins show less sequence diversity than the variable regions, and are responsible for binding a number of natural proteins to elicit important biochemical events. Each light chain has a single light chain constant region (CL) domain, which is either of the kappa or lambda type. Each heavy chain contains one or more heavy chain constant region (CH) domains that can be assigned to different classes or isotypes. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG and IgM, having heavy chains designated ex, 8, e, y and p., respectively. Full-length IgA, IgD and IgG isotypes contain CHI, CH2, CH3 and a hinge region, while IgE and IgM contain CHI, CH2, CH3 and CH4. The y and ex classes are further divided into subclasses on the basis of relatively minor differences in the CH sequence and function, e.g., humans express the following subclasses: IgGl, IgG2, IgG3, IgG4, IgAl and IgA2. IgGl antibodies can exist in multiple polymorphic variants termed allotypes (reviewed in Jefferis and Lefranc 2009. mAbs Vol 1 Issue 4 1-7) any of which are suitable. In humans there are five different classes of antibodies including IgA (which includes subclasses IgAl and IgA2), IgD, IgE, IgG (which includes subclasses IgGl, IgG2, IgG3, and IgG4), and IgM. The distinguishing features between these antibody classes are their constant, Fc regions, although subtler differences may exist in the V region. An antibody constant region can include an Fc portion. Although the boundaries of the Fc region of an immunoglobulin heavy chain might vary, the human IgG heavy-chain Fc region usually includes the region containing the CH2 and CH3 domains and the hinge region, such as an amino acid residue at position Cys226, or from Pro230, to the carboxyl-terminus thereof.

[0136] In certain embodiments, a provided antibody contains an Ig heavy chain constant domain comprising at least part of the hinge, CH2, and CH3 regions. Certain embodiments have the first heavy-chain constant region (CHI) containing the site necessary for light chain bonding, present in at least one of the fusions. DNAs encoding the immunoglobulin heavy chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host cell. This provides for greater flexibility in adjusting the mutual proportions of the three polypeptide fragments in embodiments when unequal ratios of the three polypeptide chains used in the construction provide the optimum yield of the desired fusion antibody. It is, however, possible to insert the coding sequences for two or all three polypeptide chains into a single expression vector when the expression of at least two polypeptide chains in equal ratios results in high yields or when the ratios have no significant effect on the yield of the desired chain combination.

[0137] In some embodiments, the antibody or antigen-binding fragment thereof, may contain at least a portion of an immunoglobulin constant region, such as one or more constant region domain. In some embodiments, the constant regions include a light chain constant region and/or a heavy chain constant region 1 (CHI). In some embodiments, the antibody heavy chain further includes a hinge domain, a CH2 and/or CH3 domain. In some embodiments, the Fc region is an Fc region from an IgAl, IgA2, IgD, IgE, IgGl, IgG2, IgG3, IgG4, or IgM. In some embodiments, the heavy chain constant domain is from a constant chain, or a portion thereof containing the CHI, hinge, CH2 and/or CH3, of a human IgG, such as a human IgGl or IgG4. In some embodiments, the light chain constant domain is from a constant chain of a human kappa light or lambda light chain.

[0138] In some embodiments, the heavy chain includes a variable heavy chain as described that is joined to a human constant region. In some embodiments, the human constant region includes the hinge-CHl-CH2-CH3 constant domains. In some embodiments, the human constant region is human IgGl or is derived from human IgGl, or is or is derived from a naturally occurring variant thereof. In some embodiments, the naturally occurring variant is an IgG allotype for instance with the K97R, D239E, or L241M mutation.

[0139] Among the provided antibodies are full-length antibodies containing a heavy chain with any one of the heavy chain variable regions provided herein combined with a human heavy chain constant region; and a light chain with any one of the light chain variable regions provided herein combined with a human light chain constant region. In some embodiments, the constant region of the heavy chain is a human IgGl heavy chain constant region. In some embodiments, the heavy chain constant region is set forth in SEQ ID NO: 113 or a sequence that has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 113. In some embodiments, the heavy chain constant region is set forth in SEQ ID NO: 113. In some embodiments, the constant region of the light chain is a human kappa light chain constant region. In some embodiments, the light chain constant region is set forth in SEQ ID NO: 114 or a sequence that has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 114. In some embodiments, the light chain constant region is set forth in SEQ ID NO: 114. Any of the heavy chain variable regions provided herein may be combined with a suitable human constant region. Any of the light chain variable regions may be combined with a suitable human light chain constant region.

[0140] In some embodiments, the heavy chain constant region is mutated or modified, i.e., is a modified constant region. In some embodiments, the heavy chain constant region is a modified human IgG heavy chain constant region.

[0141] In some cases, the mutations include one or more amino acid substitutions to reduce effector activity of the heavy chain constant region. In some embodiments, the heavy chain constant region is modified to reduce effector activity of the antibody. In some embodiments, the modified human IgG heavy chain constant region has reduced effector activity. In some embodiments, effector activity is reduced compared to a wild-type human IgG heavy chain constant region. In some of any of the described embodiments, the modified human IgG heavy chain constant region is modified compared to the constant region of wildtype human IgGl. In some embodiments, the modified human IgG heavy chain constant region has a sequence that is modified by one or more amino acid substitutions compared to SEQ ID NO: 113 (or a naturally occurring variant thereof, e.g. with K97R, D239E or L241M mutations) and that exhibits at least 85%, at least 90%, at least 95% or at least 98% sequence identity to SEQ ID NO: 113 or the natural variant thereof and contains the one or more amino acid substitutions, for example to reduce effector activity of the heavy chain constant region.

[0142] Various examples of mutations to heavy chain constant regions to alter, such as reduce, effector function are known, including any as described below. In some embodiments, reference to amino acid substitutions in a heavy chain constant region is by EU numbering by Kabat (also called Kabat numbering) unless described with reference to a specific SEQ ID NO. EU numbering is known and is according to the most recently updated IMGT Scientific Chart (IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org/IMGTScientificChart/Numbering/Hu_IGHGnber.html (created: 17 May 2001, last updated: 10 Jan 2013) and the EU index as reported in Kabat, E.A. et al. Sequences of Proteins of Immunological interest. 5th ed. US Department of Health and Human Services, NIH publication No. 91-3242 (1991).

[0143] The present disclosure contemplates variants of the antibodies disclosed herein. In certain embodiments, such variant antibodies or antigen-binding fragments, or CDRs thereof, bind to SLC34A2 at least about 50%, at least about 70%, at least about 80%, at least about 85%, at least about 90% and in certain embodiments, at least about 95% as well as an antibody sequence specifically set forth herein. In further embodiments, such variant antibodies or antigenbinding fragments, or CDRs thereof, bind to SLC34A2 with greater affinity than the antibodies set forth herein, for example, that bind quantitatively at least about 105%, 106%, 107%, 108%, 109%, or 110% as well as an antibody sequence specifically set forth herein.

[0144] In particular embodiments, a subject antibody may have: a) a heavy chain variable region having an amino acid sequence that is at least 80% identical, at least 85% identical, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or 99% or 100% identical, to a heavy chain variable region of an anti-SLC34A2 antibody described herein; and b) a light chain variable region having an amino acid sequence that is at least 80% identical, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or 99% or 100% identical, to a light chain variable region of an anti-SLC34A2 antibody described herein.

A. Variants and Modifications

[0145] Amino acid sequence modification(s) of the antibodies or antigen-binding fragments thereof described herein are contemplated. In certain embodiments, the antibodies or antigenbinding fragments thereof include one or more amino acid variations, e.g., substitutions, deletions, insertions, and/or mutations, compared to the sequence of an antibody or antigenbinding fragment thereof described herein. For example, it may be desirable to improve the binding affinity and/or other biological properties of the antibody or antigen-binding fragment thereof. In some embodiments, a variant antibody of a provided antibody amino acid sequence may include one or more conservative amino acid substitution in which, in some cases, the variant antibody retains similar activity or binding affinity as the sequence of any of the provided antibodies. In some embodiments, amino acid sequence variants of an antibody may be prepared by introducing appropriate nucleotide changes into a polynucleotide that encodes the antibody, or a chain thereof, or by peptide synthesis. Such modifications include, for example, deletions from, and/or insertions into and/or substitutions of, residues within the amino acid sequences of the antibody. Any combination of deletion, insertion, and substitution may be made to arrive at the final antibody, provided that the final construct possesses the desired characteristics (e.g., high affinity binding to SLC34A2). The amino acid changes may alter post-translational processes of the antibody, such as changing the number or position of glycosylation sites. Any of the variations and modifications described above for polypeptides of the present invention may be included in antibodies of the present invention.

[0146] In certain embodiments, the antibodies include one or more amino acid substitutions, e.g., as compared to an antibody sequence described herein and/or compared to a sequence of a natural repertoire, e.g., human repertoire. Sites of interest for substitutional mutagenesis include the CDRs and FRs. Amino acid substitutions may be introduced into an antibody of interest and the products screened for a desired activity, e.g., retained/improved antigen binding, decreased immunogenicity, improved half-life, and/or improved effector function, such as the ability to promote antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC).

[0147] In some embodiments, one or more residues within a CDR of a parent antibody (e.g. a humanized or human antibody) is/are substituted. In some embodiments, the substitution is made to revert a sequence or position in the sequence to a germline sequence, such as an antibody sequence found in the germline (e.g., human germline), for example, to reduce the likelihood of immunogenicity, e.g., upon administration to a human subject.

[0148] In some embodiments, alterations are made in CDR “hotspots,” residues encoded by codons that undergo mutation at high frequency during the somatic maturation process (see, e.g., Chowdhury, Methods Mol. Biol. 207:179-196 (2008)), and/or residues that contact antigen, with the resulting variant VH or VL being tested for binding affinity. Affinity maturation by constructing and reselecting from secondary libraries has been described, e.g., in Hoogenboom et al. in Methods in Molecular Biology 178:1-37 (O’Brien et al., ed., Human Press, Totowa, NJ, (2001)). In some embodiments of affinity maturation, diversity is introduced into the variable genes chosen for maturation by any of a variety of methods (e.g., error-prone PCR, chain shuffling, or oligonucleotide-directed mutagenesis). A secondary library is then created. The library is then screened to identify any antibody variants with the desired affinity. Another method to introduce diversity involves CDR-directed approaches, in which several CDR residues (e.g., 4-6 residues at a time) are randomized. CDR residues involved in antigen binding may be specifically identified, e.g., using alanine scanning mutagenesis or modeling. CDR-H3 and CDR- L3 in particular are often targeted.

[0149] In certain embodiments, substitutions, insertions, or deletions may occur within one or more CDRs so long as such alterations do not substantially reduce the ability of the antibody to bind antigen. For example, conservative alterations (e.g., conservative substitutions as provided herein) that do not substantially reduce binding affinity may be made in CDRs. Such alterations may, for example, be outside of antigen contacting residues in the CDRs. In certain embodiments of the variant VH and VL sequences provided above, each CDR either is unaltered, or contains no more than one, two or three amino acid substitutions.

[0150] Amino acid sequence insertions include amino- and/or carboxyl-terminal fusions ranging in length from one residue to polypeptides containing a hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. Examples of terminal insertions include an antibody with an N-terminal methionyl residue. Other insertional variants of the antibody molecule include the fusion to the N- or C-terminus of the antibody to an enzyme or a polypeptide which increases the serum half-life of the antibody.

[0151] Among the modified antibodies are those having one or more amino acid modifications in the Fc region, such as those having a human Fc region sequence or other portion of a constant region (e.g., a human IgGl, IgG2, IgG3 or IgG4 Fc region) comprising an amino acid modification (e.g. a substitution) at one or more amino acid positions.

[0152] Such modifications can be made, e.g., to improve half-life, alter binding to one or more types of Fc receptors, and/or alter effector functions.

[0153] Also among the variants are cysteine engineered antibodies such as “thioMAbs” and other cysteine engineered variants, in which one or more residues of an antibody are substituted with cysteine residues, in order to generate reactive thiol groups at accessible sites, e.g., for use in conjugation of agents and linker- agents, to produce immunoconjugates. Cysteine engineered antibodies are described, e.g., in U.S. Patent Nos. 7,855,275 and 7,521,541.

[0154] In some embodiments, the VH or VL of an SCL34A2 antibody or antigen-binding fragment thereof comprises a modification at the N-terminus. Recombinant monoclonal antibodies can undergo spontaneous or non-spontaneous (e.g., enzymatically catalyzed by glutaminyl cyclase) cyclization of glutamine (Q) or glutamate/glutamic acid (E) at the N- terminus, resulting in pyroglutamate (Liu et al. J Bio; Chem, volume 286:13 (2011)). In some embodiments, the N-terminal amino acid, 2 N-terminal amino acid and/or 3 N-terminal amino acid of any of the SLC34A2 antibodies provided herein are different from the N-terminal amino acid, 2 N-terminal amino acid, and/or 3 N-terminal amino acid of SEQ ID NOS: 1, 5, 9, 13, 15, 23, 27, 31, 39, 47, 51, 53, 56, 59, 66, 73, 76, 78, 82, 84, 88, 90, 93, 94 and 100, e.g., due to a post-translational modification as described above. In some embodiments, the first N-terminal Q or E of any of V_H or V_L of SEQ ID NOS: 1, 5, 9, 13, 15, 23, 27, 31, 39, 47, 51, 53, 56, 59, 66, 73, 76, 78, 82, 84, 88, 90, 93, 94 and 100 is a pyroglutamate. Provided herein are SLC34A2 antibodies, wherein if the N-terminal amino acid of the VH and/or VL amino acid sequence is Q or E, the first N-terminal amino acid residue is pyro-glutamate. Also provided are compositions comprising SLC34A2 antibodies, wherein if the N-terminal amino acid of the VH and/or VL of the antibody sequence is Q or E, at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of the antibodies in the composition have a pyro-glutamate at the first N-terminal amino acid residue of their VH and/or VL, respectively.

[0155] In some embodiments, the SCL34A2 antibody or antigen-binding fragment thereof comprises a modification at the C-terminus. C-terminal lysine modifications are found at the heavy chain C-terminus of monoclonal antibodies produced in mammalian cell cultures. In some embodiments, the C-terminus of the SLC34A2 antibodies provided herein is different from the C- terminus of SEQ ID NO: 113. In some embodiments, the C-terminus of the SLC34A2 antibodies provided herein is a lysine. In some embodiments, the C-terminus of the SLC34A2 antibodies provided herein is not a lysine. In some embodiments, the C-terminal amino acid of SEQ ID NO: 113 is a lysine. In some embodiments, the C-terminal amino acid is not a lysine.

[0156] In some embodiments, the SCL34A2 antibody or antigen-binding fragment thereof comprises a modification between the N-terminus and the C-terminus. In some embodiments, the modification comprises glycosylation, deamidation, sialylation, acetylation, phosphorylation, methylation, and glycation, among others. In some embodiments, any of SEQ ID NOS: 1, 5, 9, 13, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 53, 56, 59, 63, 66, 70, 73, 76, 78, 82, 84, 88, 90, 93, 94, 97, 100, 103, 113 and 114 comprise a modification between the N-terminus and the C-terminus. In some embodiments, the modification comprises glycosylation of an amino acid residue. In some embodiments, the modification does not comprise glycosylation of an amino acid residue.

[0157] In some embodiments, the anti-SLC34A2 antibody or antigen-binding fragment thereof is modified to remove one or more glycosylation sites. In certain embodiments, the antibody is altered to increase or decrease the extent to which the antibody is glycosylated, for example, by removing or inserting one or more glycosylation sites by altering the amino acid sequence and/or by modifying the oligosaccharide(s) attached to the glycosylation sites, e.g., using certain cell lines. [0158] In some embodiments, an N-linked glycosylation, which is a glycosylation site that occurs at asparagines in the consensus sequence -Asn-Xaa-Ser/Thr is removed or inserted. In some embodiments, one or more re replaced with another amino acid to remove the glycosylation site.

[0159] In some embodiments, the anti-SLC34A2 antibody or antigen-binding fragment thereof is an aglycosylated antibody or antigen-binding fragment thereof, which is an antibody or antigen-binding fragment thereof that lacks glycosylation. In some embodiments, the anti- SLC34A2 antibody or antigen-binding fragment thereof comprises one or more modifications, e.g., amino acid substitutions, that eliminates glycosylation at that amino acid position. Modifying an antibody to alter glycosylation can, for instance, increase the affinity of the antibody for antigen. Such carbohydrate modifications can be accomplished by, for example, altering one or more sites of glycosylation within the antibody sequence. For example, one or more amino acid substitutions can be made that result in elimination of one or more variable region framework glycosylation sites to thereby eliminate glycosylation at that site. Such aglycosylation can, in some embodiments, increase the affinity of the antibody for antigen. Such an approach is described in further detail in U.S. Patent Nos. 5,714,350 and 6,350,861 by Co et al.

[0160] Glycosylation of the constant region on N297 can, for instance, be prevented by mutating the N297 residue to another residue, e.g., N297A, and/or by mutating an adjacent amino acid, e.g., 298 to thereby reduce glycosylation on N297.

[0161] Additionally or alternatively, an antibody can be made that has an altered type of glycosylation, such as a hypofucosylated antibody having reduced amounts of fucosyl residues or an antibody having increased bisecting GlcNac structures. Such altered glycosylation patterns have been demonstrated to increase the ADCC ability of antibodies. Such carbohydrate modifications can be accomplished by, for example, expressing the antibody in a host cell with altered glycosylation machinery. Cells with altered glycosylation machinery have been described in the art and can be used as host cells in which to express recombinant antibodies described herein to thereby produce an antibody with altered glycosylation, such as in methods for antibody production as described herein. For example, EP 1,176,195 by Hanai et al. describes a cell line with a functionally disrupted FUT8 gene, which encodes a fucosyl transferase, such that antibodies expressed in such a cell line exhibit hypofucosylation. WO 03/035835 describes a variant CHO cell line, Led 3 cells, with reduced ability to attach fucose to Asn(297)-linked carbohydrates, also resulting in hypofucosylation of antibodies expressed in that host cell (see also Shields, R.L. et al. (2002) J. Biol. Chem. 277:26733-26740). WO 99/54342 describes cell lines engineered to express glycoprotein-modifying glycosyl transferases (e.g., beta(l,4)-N- acetylglucosaminyltransferase III (GnTIII)) such that antibodies expressed in the engineered cell lines exhibit increased bisecting GlcNac structures which results in increased ADCC activity of the antibodies (see also Umana et al. (1999) Nat. Biotech. 17: 176-180).

[0162] Exemplary modifications, variants, and cell lines are described, e.g., in Patent Publication Nos. US 2003/0157108, US 2004/0093621, US 2003/0157108; WO 2000/61739; WO 2001/29246; US 2003/0115614; US 2002/0164328; US 2004/0093621; US 2004/0132140; US 2004/0110704; US 2004/0110282; US 2004/0109865; WO 2003/085119; WO 2003/084570; WO 2005/035586; WO 2005/035778; W02005/053742; W02002/031140; Okazaki et al. J. Mol. Biol. 336:1239-1249 (2004); Yamane-Ohnuki et al. Biotech. Bioeng. 87: 614 (2004). Ripka et al. Arch. Biochem. Biophys. 249:533-545 (1986); US Pat Appl No US 2003/0157108 Al, Presta, L; and WO 2004/056312 Al, Yamane-Ohnuki et al. Biotech. Bioeng. 87: 614 (2004); Kanda, Y. et al., Biotechnol. Bioeng., 94(4):680-688 (2006); and W02003/085107); WO 2003/011878 (Jean- Mairet et al.); US Patent No. 6,602,684 (Umana et al.); and US 2005/0123546 (Umana et al.); WO 1997/30087 (Patel et al.); WO 1998/58964 (Raju, S.); and WO 1999/22764 (Raju, S.).

B. Exemplary features

[0163] In some aspects, the provided antibodies have one or more specified functional features, such as binding properties, including binding to particular epitopes or exhibiting lower or reduced binding to a related but non-specific antigen. In some aspects, the provided antibodies can bind to an epitope that is similar to or overlaps with epitopes of other antibodies, such as reference antibodies, and/or exhibit particular binding affinities. In some aspects, the provided antibodies can bind to an epitope that is different from epitopes of other antibodies, e.g., binding a conformational epitope.

[0164] In some embodiments, the provided antibodies or antigen-binding fragment thereof specifically bind to SLC34A2. In some of any of the embodiments provided herein, SLC34A2 refers to human SLC34A2. The observation that an antibody or other binding molecule binds to SLC34A2 or specifically binds to SLC34A2 does not necessarily mean that it binds to SLC34A2 from every species. For example, in some embodiments, features of binding to SLC34A2, such as the ability to specifically bind thereto and/or to compete for binding thereto with a reference antibody, and/or to bind with a particular affinity or compete to a particular degree, in some embodiments, refers to the ability with respect to a human SLC34A2 and the antibody may not have this feature with respect to an SLC34A2 of another species such as mouse. In some embodiments, the antibody binds to human SLC34A2 and binds to SLC34A2 of another species, such as Rhesus macaque or cynomolgus macaque.

[0165] In some embodiments, the antibodies, such as the anti-SLC34A2 antibodies, e.g., the human antibodies, specifically bind to a particular epitope or region of SLC34A2, such as generally an extracellular epitope or region. In some embodiments, the antibodies or antigenbinding fragment thereof bind, such as specifically bind, to human SLC34A2, such as to one or more epitopes or region of human SLC34A2, or an allelic variant or splice variant thereof. In some embodiments, the antibodies or antigen-binding fragment thereof specifically binds to one or more epitopes within a human SLC34A2.

[0166] In some embodiments, the antibodies specifically bind to human SLC34A2 protein, such as to an epitope or region of human SLC34A2 protein, such as the human SLC34A2 protein comprising the amino acid sequence of SEQ ID NO:111 (Uniprot 095436, encoded by a sequence comprising SEQ ID NO: 112 or SEQ ID NO: 188), or an allelic variant or splice variant thereof. In some embodiments, the antibodies specifically bind to SEQ ID NO: 108. In some embodiments, the antibodies specifically bind to SEQ ID NO: 109. In some embodiments, the antibodies specifically bind to SEQ ID NO: 115. In some embodiments, the antibodies specifically bind to SEQ ID NO: 106. In some embodiments, the antibodies specifically bind to an SLC34A2 protein that is conjugated to a peptide that enhances immunogenicity. In some embodiments, the peptide comprises KLH. In some embodiments, the KLH comprises an amino acid sequence set forth in SEQ ID NO: 107.

[0167] In some embodiments, the antibodies or antigen-binding fragment thereof bind one or more epitopes of SLC34A2, such as a human SLC34A2. In some embodiments, the antibodies or antigen-binding fragment thereof bind a linear epitope of SLC34A2, such as a human SLC34A2. In some embodiments, the antibodies or antigen-binding fragment thereof bind one or more conformational epitopes of SLC34A2, such as a human SLC34A2.

[0168] In some embodiments, the antibody binds to non-human SLC34A2, such as Rhesus macaques (Macaco mulatto) or cynomolgus macaques (Macaco fasicularis). In some embodiments, the antibody binds to non-human SLC34A2, such as monkey, rabbit, rat, mouse, or other species of SLC34A2. In some embodiments, the antibody binds to mouse (Mus musculus) SLC34A2, such as to an epitope or region of mouse SLC34A2. In some embodiments, the antibody binds to human SLC34A2 and binds to mouse SLC34A2. In some of any of the provided embodiments, the antibody or antigen-binding fragment thereof does not bind to, is not cross -reactive to, or binds at a lower extent, level or degree or affinity to a non-human SLC34A2. [0169] Competitive inhibition assays are known and include ELISA-based, flow cytometrybased assays, and RIA-based assays. In some aspects, competitive inhibition assays are carried out by incorporating an excess of an unlabeled form of one of the antibodies and assessing its ability to block binding of the other antibody, which is labeled with a detectable marker, such that degree of binding and reduction thereof can be assessed by detection of the label or marker. In some embodiments, addition of the provided antibody in excess, e.g., 1-, 2-, 5-, 10-, 50- or 100- fold excess, as compared to the amount or concentration of the reference antibody, inhibits binding to the antigen by the reference antibody (or vice versa). In some embodiments, the inhibition of binding is by at least 50%, and in some embodiments by at least 75%, 90% or 99%. In some aspects, the competitive inhibition is as measured in a competitive binding assay (see, e.g., Junghans et al., Cancer Res. 1990:50:1495-1502). Competition assays may be used to identify an antibody that competes with any of the antibodies described herein. Assays for mapping epitopes bound by the antibodies and reference antibodies also may be used and are known.

[0170] Anti-SLC34A2 antibodies provided herein may be identified, screened for, or characterized for their physical/chemical properties and/or biological activities by various known assays. In one aspect, the antibody is tested for its antigen binding activity, e.g., by known methods such as ELISA, Western blotting, and/or flow cytometric assays, including cell-based binding assays, for example, assessing binding of the antibody (e.g., conjugated to a fluorescent marker or tagged) to a cell expressing the target antigen, e.g., SLC34A2, in some cases compared to results using cells that do not express the target antigen, e.g., SLC34A2 In some embodiments, the cell expressing SLC34A2 is an OVCAR3 cells. Binding affinity may be measured as KD, KA or EC50. In some embodiments, the EC50 value is based on binding of any of the anti-SLC34A2 antibodies provided herein to SLC34A2 expressed on OVCAR3 cells.

[0171] In some embodiments, the provided antibodies are capable of binding SLC34A2, such as human SLC34A2, with at least a certain affinity, as measured by any of a number of known methods. In some embodiments, the affinity is represented by an equilibrium dissociation constant (KD). In some embodiments, the affinity is represented by EC50.

[0172] A variety of assays are known for assessing binding affinity, equilibrium dissociation constant (KD), equilibrium association constant (KA), EC50, on-rate (association rate constant; k_on or k_a; units of 1/Ms or M^s'¹) and the off-rate (dissociation rate constant; k_off or ka; units of 1/s or s'¹) and/or determining whether a binding molecule (e.g., an antibody or fragment thereof) specifically binds to a particular ligand (e.g., an antigen, such as SLC34A2). One can determine the binding affinity of a binding molecule, e.g., an antibody or an antigen-binding fragment thereof, for an antigen, e.g., SLC34A2, such as human SLC34A2 or cynomolgus SLC34A2 or mouse SLC34A2, such as by using any of a number of binding assays that are well known. For example, in some embodiments, a BIAcore® instrument can be used to determine the binding kinetics and constants of a complex between two proteins (e.g., an antibody or fragment thereof, and an antigen, such as SLC34A2), using surface plasmon resonance (SPR) analysis (see, e.g., Scatchard et al., Ann. N.Y. Acad. Sci. 51:660, 1949; Wilson, Science 295:2103, 2002; Wolff et al., Cancer Res. 53:2560, 1993; and U.S. Patent Nos. 5,283,173, 5,468,614, or the equivalent).

[0173] In some embodiments, the binding affinity (EC50) and/or the equilibrium dissociation constant, KD, of the binding molecule, e.g., anti-SLC34A2 antibody or fragment thereof, to SLC34A2, such as human SLC34A2, is from at or about 0.01 nM to about 1 pM, 0.1 nM to 1 pM, 1 nM to 1 pM, 1 nM to 500 nM, 1 nM to 100 nM, 1 nM to 50 nM, 1 nM to 10 nM, 10 nM to 500 nM, 10 nM to 100 nM, 10 nM to 50 nM, 50 nM to 500 nM, 50 nM to 100 nM or 100 nM to 500 nM. In certain embodiments, the binding affinity (EC50) and/or the equilibrium dissociation constant, KD, of the binding molecule, e.g., anti-SLC34A2 antibody or fragment thereof, to SLC34A2, such as a human SLC34A2, is at or about or less than at or about 1 pM, 500 nM, 100 nM, 50 nM, 40 nM, 30 nM, 25 nM, 20 nM, 19 nM, 18 nM, 17 nM, 16 nM, 15 nM, 14 nM, 13 nM, 12 nM, 11 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, or 1 nM or less, or a range defined by any of the foregoing.

[0174] In some embodiments, the binding affinity (EC50) and/or the equilibrium dissociation constant (KD) of the antibody to SLC34A2, such as human SLC34A2, is from at or about 0.1 nM to at or about 500 nM, from at or about 0.1 nM to at or about 50 nM, from at or about 0.1 nM to at or about 40 nM, from at or about 0.1 nM to at or about 30 nM, from at or about 0.1 nM to at or about 20 nM, from at or about 0.1 nM to at or about 10 nM, from at or about 0.1 nM to at or about 1 nM, from at or about 1 nM to at or about 500 nM, from at or about 1 nM to at or about 50 nM, from at or about 1 nM to at or about 40 nM, from at or about 1 nM to at or about 30 nM, from at or about 1 nM to at or about 20 nM, from at or about 1 nM to at or about 10 nM, from at or about 10 nM to at or about 500 nM, from at or about 10 nM to at or about 50 nM, from at or about 10 nM to at or about 40 nM, from at or about 10 nM to at or about 30 nM, or from at or about 10 nM to at or about 20 nM. In certain embodiments, the binding affinity (EC50) and/or the equilibrium dissociation constant (KD) of the antibody to SLC34A2, such as human SLC34A2, is at or about or less than at or about 50 nM, 40 nM, 30 nM, 25 nM, 20 nM, 19 nM, 18 nM, 17 nM, 16 nM, 15 nM, 14 nM, 13 nM, 12 nM, 11 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, or 1 nM, or a range defined by any of the foregoing.

[0175] In some embodiments, the antibodies bind to SLC34A2, such as human SLC34A2, with a sub-nanomolar binding affinity, for example, with a binding affinity less than at or about 1 nM, such as less than at or about 0.9 nM, 0.8 nM, 0.7 nM, 0.6 nM, 0.5 nM, 0.4 nM, 0.3 nM, 0.2 nM or 0.1 nM.

[0176] In some embodiments, among desired antibodies that bind to SLC34A2, such as human SLC34A2, are those with a nanomolar binding affinity for binding to SLC34A2. In some embodiments, an anti- SLC34A2 antibody exhibits a binding affinity (Kd) that is greater than 5 nM. In some embodiments, an anti- SLC34A2 antibody exhibits a binding affinity (Kd) that is greater than 10 nM. In some embodiments, the Kd of an anti- SLC34A2 antibody is at or about 5 nM, 7.5 nM, 10 nM, 15 nM, 20 nM, 25 nM, 30 nM, 40 nM, 50 nM, 60 nM, 70 nM, 80 nM, 90 nM, 100 nM, or any value between any of the foregoing. In some embodiments, the Kd of an anti- SLC34A2 antibody is between 5 nM and 70 nM. In some embodiments, the Kd of an anti¬

CD3 antibody is between 10 nM and 60 nM. In some embodiments, the Kd of an anti- SLC34A2 antibody is between 20 nM and 50 nM. In some embodiments, the Kd of an anti- SLC34A2 antibody is between 10 nM and 70 nM. In some embodiments, the Kd of an anti- SLC34A2 antibody is between 20 nM and 30 nM. In some embodiments, the Kd of an anti- SLC34A2 antibody is between 5 nM and 20 nM. In some embodiments, the Kd of an anti- SLC34A2 antibody is between 5 nM and 15 nM. In some embodiments, the Kd of an anti- SLC34A2 antibody is between 5 nM and 10 nM.

[0177] In some embodiments, the antibodies display a binding preference for SLC34A2- expressing cells as compared to SLC34A2-negative cells, such as particular cells known and/or described herein to express SLC34A2 compared to cells known not to express SLC34A2. In some embodiments, the binding preference is observed where a significantly greater degree of binding is measured to the SLC34A2-expressing, as compared to the non-expressing cells or cells expressing a related but different antigen. In some embodiments, the fold change in degree of binding detected, for example, as measured by mean fluorescence intensity in a flow cytometrybased assay and/or dissociation constant or EC50, to the SLC34A2-expressing cells as compared to the non- SLC34A2-expressing cells or cells expressing a related but different antigen, is at least at or about 1.5, 2, 3, 4, 5, 6, or more, and/or is about as great, about the same, at least as great or at least about as great, or greater, than the fold change observed for the corresponding form of the reference antibody. In some cases, the total degree of observed binding to SLC34A2 or to the SLC34A2-expressing cells is approximately the same, at least as great, or greater than that observed for the corresponding form of the reference antibody. In some embodiments, the SLC34A2-expressing cell is a cell associated with a disease or condition. In some embodiments, the SLC34A2-expressing cell is a cancer cell. In some embodiments, the SLC34A2-expressing cell is a blood cancer cell. In some embodiments, the SLC34A2-expressing cell is a solid tumor cell. In some embodiments, the solid tumor cell is malignant.

[0178] In some aspects, the affinity is at or about the same degree or substantially the same degree of affinity compared to the corresponding form of the reference antibody, such as rabbit SLC34A2 antibody. In some aspects, the affinity is at least at or about 80, 85, 90, 95, or 99% of or the same as that of the corresponding form of the reference antibody.

[0179] In some embodiments, the antibody specifically binds to an epitope that overlaps with the epitope of SLC34A2 bound by a reference antibody. In some aspects, among such antibodies are antibodies that bind to the same or a similar epitope as the reference antibody. In some embodiments, the antibodies bind to the same or a similar epitope or an epitope within the same region or containing residues within the same region of SLC34A2 as a reference antibody. In some embodiments, the antibody inhibits binding to and/or competes for binding to SLC34A2, such as human SLC34A2, with the reference antibody.

III. SLC34A2-BINDING MOLECULES

[0180] Provided herein are binding molecules comprising any of the provided antibodies or antigen-binding fragments.

[0181] In some embodiments, the binding molecules can include fusion proteins by amino acid sequence insertions that include amino- and/or carboxyl-terminal fusions ranging in length from one residue to polypeptides containing a hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. Examples of terminal insertions include an antibody with an N-terminal methionyl residue. Other insertional variants of the antibody molecule include the fusion to the N- or C-terminus of the antibody to an enzyme or a polypeptide which increases the serum half-life of the antibody.

[0182] In some embodiments, binding molecules include an anti-SLC34A2 antibody or antigen-binding fragment thereof that is modified to improve half-life.

[0183] In some embodiments, the antibodies or antigen-binding fragments thereof are modified to contain additional nonproteinaceous moieties, including water soluble polymers. Exemplary polymers include, but are not limited to, polyethylene glycol (PEG), copolymers of ethylene glycol/propylene glycol, carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, poly-1, 3-dioxolane, poly-l,3,6-trioxane, ethylene/maleic anhydride copolymer, poly aminoacids (either homopolymers or random copolymers), and dextran or poly(n-vinyl pyrrolidone)polyethylene glycol, propropylene glycol homopolymers, prolypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof. Polyethylene glycol propionaldehyde may have advantages in manufacturing due to its stability in water. The polymer may be of any molecular weight, and may be branched or unbranched. The number of polymers attached to the antibody may vary, and if more than one polymer is attached, they can be the same or different molecules. In general, the number and/or type of polymers used for derivatization can be determined based on considerations including, but not limited to, the particular properties or functions of the antibody to be improved, whether the antibody derivative will be used in a therapy under defined conditions, etc.

[0184] In some embodiments, binding molecules include an anti-SLC34A2 antibody or antigen-binding fragment thereof provided herein that are modified by pegylation. Accordingly, in some embodiments, the anti-SLC34A2 antibodies or antigen-binding fragments thereof is pegylated. An antibody can be pegylated to, for example, increase the biological (e.g., serum) half-life of the antibody. In some embodiments, the antibody or antigen-binding fragment thereof is pegylated by reacting it with polyethylene glycol (PEG), such as a reactive ester or aldehyde derivative of PEG, under conditions in which one or more PEG groups become attached to the antibody or antibody fragment. In some embodiments, the pegylation is carried out via an acylation reaction or an alkylation reaction with a reactive PEG molecule (or an analogous reactive water-soluble polymer). As used herein, the term “polyethylene glycol” is intended to encompass any of the forms of PEG that have been used to derivatize other proteins, such as mono (CI-CIO) alkoxy- or aryloxy-polyethylene glycol or polyethylene glycol-maleimide. In certain embodiments, the antibody to be pegylated is an aglycosylated antibody. Methods for pegylating proteins are known in the art and can be applied to the antibodies described herein. See, e.g., EP 0 154 316 by Nishimura et al. and EP 0401 384 by Ishikawa et al.

[0185] In some embodiments, provided herein are binding molecules in which a provided antibody or antigen-binding fragment is a cysteine engineered antibody such as “thioMAbs” or another cysteine engineered variants, in which one or more residues of an antibody are substituted with cysteine residues, in order to generate reactive thiol groups at accessible sites, e.g., for use in conjugation of agents and linker- agents, to produce immunoconjugates. Cysteine engineered antibodies are described, e.g., in U.S. Patent Nos. 7,855,275 and 7,521,541.

[0186] Antibodies, and antigen-binding fragments and variants thereof, of the present invention may also be modified to include a detectable label, e.g., an epitope tag or label, e.g., for use in purification or diagnostic applications. These may be conjugated to the antibody as a fusion protein or conjugate, e.g., using a linker or linking group. There are many linking groups known in the art for making antibody conjugates, including, for example, those disclosed in U.S. Pat. No. 5,208,020 or EP Patent 0 425 235 Bl, and Chari et al., Cancer Research 52: 127-131 (1992). Linking groups include disulfide groups, thioester groups, acid labile groups, photolabile groups, peptidase labile groups, or esterase labile groups, as disclosed in the above-identified patents. Examples of tags and/or labels can include, but are not limited to, FLAG tags, polyhistidine tags (e.g. 6xHis), cMyc tags, glutathione-S-transferase tags, avidin, fluorescent labels, polymer particles, metal particles, haptens, enzyme labels, luminescent labels, electrochemiluminescent labels, bioluminescent labels, radioisotopes, or oligonucleotides.

[0187] In some embodiments, the binding molecules include but are not limited to immunoconjugates, multispecific antibodies, chimeric antigen receptors (CAR), or synthetic receptors such as synthetic transcriptional modulator receptors.

A. Conjugates

[0188] Provided herein are conjugates containing an anti-SLC34A2 antibody or antigenbinding fragment provided herein and one or more further moiety. The further moiety can be an effector moiety, which provides at least one additional function or property of the conjugate as compared to the unconjugated antibody. In some embodiments, an effector moiety can be any substance having biological or detectable activity, for example, therapeutic agents, detectable labels, binding agents, or prodrugs, which are metabolized to an active agent in vivo. In some embodiments, the moiety can be a targeting moiety, a small molecule drug (non-polypeptide drug of less than 500 Daltons molar mass), a toxin, a cytostatic agent, a cytotoxic agent, an immunosuppressive agent, a radioactive agent suitable for diagnostic purposes, a radioactive metal ion for therapeutic purposes, a prodrug-activating enzyme, an agent that increases biological half-life, or a diagnostic or detectable agent. In some embodiments, the effector moiety is a protein, peptide or a nucleic acid molecule, which can be synthesized or produced by recombinant means. In some embodiments, the effector moiety is a drug moiety, which may be synthesized artificially or purified from a natural source. [0189] In some embodiments, the drug moiety has an intracellular activity. In some embodiments, the anti-SLC34A2 antibody or antigen-binding fragment of the conjugate is internalized and the drug moiety is a cytotoxin that blocks the protein synthesis of the cell, therein leading to cell death. The conjugate can be used for inhibiting the multiplication of a tumor cell or cancer cell, causing apoptosis in a tumor or cancer cell, or for treating cancer in a patient. The conjugate can be used accordingly in a variety of settings for the treatment of animal cancers. The conjugate can be used to deliver a drug to a tumor cell or cancer cell. In some embodiments, upon binding to SLC34A2 on a tumor cell, the conjugate and/or drug can be taken up inside a tumor cell or cancer cell through receptor-mediated endocytosis.

[0190] In some embodiments, the conjugate is an antibody drug conjugate (ADC, also called immunoconjugates) containing an anti-SLC34A2 antibody or antigen-binding fragment provided herein conjugated to a drug moiety that acts as a therapeutic agent, which is either cytotoxic, cytostatic or otherwise provides some therapeutic benefit. In some embodiments, the cytotoxic agent is a chemotherapeutic agent, a drug, a growth inhibitory agent, a toxin (e.g., an enzymatically active toxin of bacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate). In some embodiments, provided antibody drug conjugates of the present disclosure allow targeted-delivery of the drug moiety to tumors. In some cases, this can result in targeted killing of the tumor cell.

[0191] In some embodiments, the drug moiety is an auristatin, such as auristatin E (also known in the art as a derivative of dolastatin-10) or a derivative thereof. The auristatin can be, for example, an ester formed between auristatin E and a keto acid. For example, auristatin E can be reacted with paraacetyl benzoic acid or benzoylvaleric acid to produce AEB and AEVB, respectively. Other typical auristatins include AFP, MMAF, and MMAE. The synthesis and structure of exemplary auristatins are described in U.S. Pat. Nos. 6,884,869, 7,098,308, 7,256,257, 7,423,116, 7,498,298 and 7,745,394, each of which is incorporated by reference herein in its entirety and for all purposes.

[0192] Auristatins have been shown to interfere with microtubule dynamics and nuclear and cellular division and have anticancer activity. Auristatins of the present invention bind tubulin and can exert a cytotoxic or cytostatic effect on a 5T4 expressing cell or cell line. There are a number of different assays, known in the art, that can be used for determining whether an auristatin or resultant antibody-drug conjugate exerts a cytostatic or cytotoxic effect on a desired cell or cell line. Methods for determining whether a compound binds tubulin are known in the art. See, for example, Muller et al., Anal. Chem 2006, 78, 4390-4397; Hamel et al., Molecular Pharmacology, 1995 47: 965-976; and Hamel et al., The Journal of Biological Chemistry, 1990 265:28, 17141-17149.

[0193] Examples of drugs or pay loads are selected from the group consisting of DM1 (maytansine, N2'-deacetyl-N2'-(3-mercapto-l-oxopropyl)- or N2'-deacetyl-N2'-(3-mercapto-l- oxopropyl)-may tansine), mc-MMAD (6-maleimidocaproyl-monomethylauristatin-D or N- methyl-L-valyl-N- [( 1 S,2R)-2-methoxy-4- [(2S)-2- [( 1R,2R)- 1 -methoxy-2-methyl-3-oxo-3- [[( 1 S)- 2-phenyl- 1 -(2-thiazolyl)ethyl] amino]propyl] - 1 -pyrrolidinyl] -1-[(1S)-1 -methylpropyl] -4- oxobutyl]-N-methyl-(9Cl)-L-valinamide), mc-MMAF (maleimidocaproyl-monomethylauristatin F or N- [ 6 - (2 , 5 -dihydro-2, 5-dioxo- 1 H-pyrrol- 1 -yl)- 1 -oxohexyl] -N -methyl-E-valyl-E-valyl- (3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoyl-(aR,pR,2S)-P-methoxy-a-methyl-2- pyrrolidinepropanoyl-E-phenylalanine) and mc-Val-Cit-PABA-MMAE (6-maleimidocaproyl- ValcCit-(p-aminobenzyloxycarbonyl)-monomethylauristatin E or N-[[[4-[[N-[6-(2,5-dihydro-2,5- dioxo-lH-pyrrol-l-yl)-l-oxohexyl]-L-valyl-N5-(aminocarbonyl)-L- omithyl]amino]phenyl]methoxy]carbonyl]-N-methyl-L-valyl-N-[(lS,2R)-4-[(2S)-2-[(lR,2R)-3- [[( 1 R,2S)-2-hydroxy- 1 -methyl-2-phenylethyl] amino] - 1 -methoxy-2-methyl-3-oxopropyl] - 1 - pyrrolidinyl] -2-methoxy- 1-[(1S)-1 -methylpropyl] -4-oxobutyl] -N-methyl-L- valinamide) . DM 1 is a derivative of the tubulin inhibitor maytansine while MMAD, MMAE, and MMAF are auristatin derivatives. The preferred pay loads of the present invention are selected from the group consisting of mc-MMAF and mc-Val-Cit-PABA-MMAE.

[0194] In a further embodiment, the drug moiety is an anti-cancer agent. Exemplary anticancer agents include, but are not limited to, cytostatics, enzyme inhibitors, gene regulators, cytotoxic nucleosides, tubulin binding agents or tubulin inhibitors, proteasome inhibitors, hormones and hormone antagonists, anti-angiogenesis agents, and the like. Exemplary cytostatic anti-cancer agents include alkylating agents such as the anthracycline family of drugs (e.g. adriamycin, carminomycin, cyclosporin-A, chloroquine, methopterin, mithramycin, porfiromycin, streptonigrin, porfiromycin, anthracenediones, and aziridines). Other cytostatic anti-cancer agents include DNA synthesis inhibitors (e.g., methotrexate and dichloromethotrexate, 3-amino- 1,2,4- benzotriazine 1,4-dioxide, aminopterin, cytosine P-D-arabinofuranoside, 5-fluoro-5'- deoxyuridine, 5-fluorouracil, ganciclovir, hydroxyurea, actinomycin-D, and mitomycin C), DNA- intercalators or cross-linkers (e.g., bleomycin, carboplatin, carmustine, chlorambucil, cyclophosphamide, cis-diammineplatinum(II) dichloride (cisplatin), melphalan, mitoxantrone, and oxaliplatin), and DNA-RNA transcription regulators (e.g., actinomycin D, daunorubicin, doxorubicin, homoharringtonine, and idarubicin). Other exemplary cytostatic agents that are compatible with the present disclosure include ansamycin benzoquinones, quinonoid derivatives (e.g. quinolones, genistein, bactacyclin), busulfan, ifosfamide, mechlorethamine, triaziquone, diaziquone, carbazilquinone, indoloquinone EO9, diaziridinyl-benzoquinone methyl DZQ, triethylenephosphoramide, and nitrosourea compounds (e.g. carmustine, lomustine, semustine).

[0195] In some embodiments, there is provided a conjugate comprising anti-SLC34A2 antibody or antigen-binding fragment provided herein conjugated with a toxin. In some embodiments, the therapeutic agent is a cytotoxin comprising a polypeptide having ribosomeinactivating activity including, for example, gelonin, bouganin, saporin, ricin, ricin A chain, bryodin, diphtheria toxin, restrictocin, Pseudomonas exotoxin A and variants thereof.

[0196] In some embodiments, the effector moiety is a radionuclide (e.g., a peptide receptor radionuclide) or a radiolabel. In some embodiments, the effector moiety is a radionuclide or radiolabel with high-energy ionizing radiation that are capable of causing multiple strand breaks in nuclear DNA, leading to cell death. Exemplary high-energy radionuclides include: 90Y, 1251, 1311, 1231, U lin, 105Rh, 153Sm, 67Cu, 67Ga, 166Ho, 177Lu, 186Re and 188Re. These isotopes typically produce high energy a- or P-particles which have a short path length. Such radionuclides kill cells to which they are in close proximity, for example neoplastic cells to which the conjugate has attached or has entered. They have little or no effect on non-localized cells and are essentially non-immunogenic. Alternatively, high-energy isotopes may be generated by thermal irradiation of an otherwise stable isotope, for example as in boron neutron-capture therapy (Guan et al., PNAS, 95: 13206-10, 1998).

[0197] In some embodiments, there is provided a conjugate comprising an anti-SLC34A2 antibody or antigen-binding fragment provided herein conjugated with a label, which can generate a detectable signal, indirectly or directly. These conjugates can be used for research or diagnostic applications, such as for the in vivo detection of cancer. The label is preferably capable of producing, either directly or indirectly, a detectable signal. For example, the label may be radio-opaque or a radioisotope, such as 3H, 14C, 32P, 35S, 1231, 1251, 1311; a fluorescent (fluorophore) or chemiluminescent (chromophore) compound, such as fluorescein isothiocyanate, rhodamine or luciferin; an enzyme, such as alkaline phosphatase, P-galactosidase or horseradish peroxidase; an imaging agent; or a metal ion. In some embodiments, the label is a radioactive atom for scintigraphic studies, for example 99Tc or 1231, or a spin label for nuclear magnetic resonance (NMR) imaging (also known as magnetic resonance imaging, MRI), such as zirconium-89, iodine-123, iodine-131, indium-i l l, fluorine-19, carbon-13, nitrogen-15, oxygen- 17, gadolinium, manganese or iron. Zirconium-89 may be complexed to various metal chelating agents and conjugated to antibodies, e.g., for PET imaging (WO 2011/056983).

[0198] The conjugates may be prepared using any methods known in the art. See, e.g., WO 2009/067800, WO 2011/133886, and U.S. Patent Application Publication No. 2014322129, incorporated by reference herein in their entirety.

[0199] In some embodiments, the linkage of an antibody or antigen binding fragment to a moiety, such as a drug or toxin or other heterologous moiety, is a direct or indirect linkage. In some embodiments, the attachment can be covalent or non-covalent, e.g., via a biotin-streptavidin non-covalent interaction. For example, a moiety can be attached by alkylation (e.g., at the epsilon-amino group lysines or the N-terminus of antibodies), reductive amination of oxidized carbohydrate, transesterification between hydroxyl and carboxyl groups, amidation at amino groups or carboxyl groups, and conjugation to thiols. In some embodiments, the attachment of a moiety, such as a therapeutic agent, can be by chemical conjugation and linkage methods known in the art. In some embodiments, the moiety can be linked to an antibody by a linker. In some embodiments, linkers such as peptide linkers, cleavable linkers, non-cleavable linkers or linkers that aid in the conjugation reaction, can be used to link or conjugate the effector moieties to the antibody or antigen-binding fragment. Attachment of a linker to an antibody can be accomplished in a variety of ways, such as through surface lysines, reductive-coupling to oxidized carbohydrates, and through cysteine residues liberated by reducing interchain disulfide linkages. A variety of antibody drug conjugate linkage systems are known in the art, including hydrazone-, disulfide- and peptide-based linkages.

[0200] In some embodiments, an anti-SLC34A2 antibody or antigen-binding fragment provided herein is conjugated to one or more moieties, e.g. about 1 to about 20 drug moieties, through a linker (L). In some embodiments, the conjugate comprises the following components: (antibody or antigen-binding fragment), (L)_q and (moiety)_m, wherein the antibody or antigenbinding fragment is any of the described capable of specifically binding SLC34A2 as described; L is a linker for linking the protein or polypeptide to the moiety; m is at least 1; q is 0 or more; and the resulting conjugate binds to SLC34A2. In particular embodiments, m is 1 to 4 and q is 0 to 8.

[0201] The linker may be composed of one or more linker components. For covalent attachment of the antibody and the drug moiety the linker typically has two reactive functional groups, i.e. bivalency in a reactive sense. Bivalent linker reagents which are useful to attach two or more functional or biologically active moieties, such as peptides, nucleic acids, drugs, toxins, antibodies, haptens, and reporter groups are known, and methods have been described their resulting conjugates (Hermanson, G. T. (1996) Bioconjugate Techniques; Academic Press: New York, p 234-242).

[0202] In some embodiments, the linker may comprise amino acid residues. Exemplary amino acid linker components include a dipeptide, a tripeptide, a tetrapeptide or a pentapeptide. Exemplary dipeptides include: valine-citrulline (vc or val-cit), alanine-phenylalanine (af or ala- phe). Exemplary tripeptides include: glycine- valine-citrulline (gly-val-cit) and glycine-glycine- glycine (gly-gly-gly). Amino acid residues which comprise an amino acid linker component include those occurring naturally, as well as minor amino acids and non-naturally occurring amino acid analogs, such as citrulline. Amino acid linker components can be designed and optimized in their selectivity for enzymatic cleavage by a particular enzymes, for example, a tumor-associated protease, cathepsin B, C and D, at a plasmin protease.

[0203] Exemplary linker components include 6-maleimidocaproyl (“MC”), maleimidopropanoyl (“MP”), valine-citrulline (“val-cit”), a alanine-phenylalanine (“ala-phe”), p- aminobenzyloxycarbonyl (“PAB”), N-Succinimidyl 4-(2-pyridylthio)pentanoate (“SPP”), N- Succinimidyl 4-(N-maleimidomethyl)cyclohexane-I carboxylate (“SMCC”), and N-Succinimidyl (4-iodo-acetyl)aminobenzoate (“SLAB”).

[0204] Conjugates of an anti-SLC34A2 antibody or antigen-binding fragment provided herein and cytotoxic agent can be made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HC1), active esters (such as disuccinimidyl substrate), aldehydes (such as glutaraldehyde), bis-azido compounds (such as bis(p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p- diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as toluene 2,6-diisocyanate), and bisactive fluorine compounds (such as l,5-difluoro-2,4-dinitrobenzene).

[0205] The antibody drug conjugate can be prepared by a variety of methods, such as organic chemistry reactions, conditions, and reagents known to those skilled in the art. Alternatively, a fusion protein containing an antibody or antigen-binding fragment and cytotoxic agent may be made, e.g., by recombinant techniques or peptide synthesis. The length of DNA may comprise respective regions encoding the two portions of the conjugate either adjacent one another or separated by a region encoding a linker peptide which does not destroy the desired properties of the conjugate B. Multispecific Antibodies

[0206] Provided herein are SLC34A2-binding polypeptides that are multispecific containing at least one antibody or antigen-binding fragment that binds SLC34A2 and one or more additional binding domains. Typically, the one or more additional domains bind to a second antigen or protein other than SLC34A2. In some aspects, the further antigen or protein may be an antigen expressed on a tumor, a molecule or receptor expressed on an immune cell, such as a T cell, e.g. a CD3, or an additional inhibitory receptor (e.g. CTLA-4, LAG3, TIM3, VISTA, TIGIT, SIRPa, NKG2A, B7H3, B7H4) or an activating receptor (e.g. 0X40, GITR, 41BB, CD40, CD27, CD28 or ICOS) or to confer an additional specificity to a target cell (e.g. CD8 or CD4). In some embodiments, the one or more additional domain is an antibody or antigen-binding fragment specific for the second antigen or protein.

[0207] In some embodiments, a provided binding molecule is a bispecific T cell engager that is composed of a SLC34A2 antibody or antigen-binding fragment as described herein and at least one additional binding molecule capable of binding to a surface molecule expressed on a T cell. In some embodiments, the surface molecule is an activating component of a T cell, such as a component of the T cell receptor complex. In particular aspects, the surface molecule is an activating T cell antigen that is expressed on a T cell and is capable of inducing T cell activation upon interaction with an antigen binding molecule. For example, in some aspects, interaction of an antigen binding molecule with an activating T cell antigen may induce T cell activation by triggering the signaling cascade of the T cell receptor complex. Suitable assays to measure T cell activation are known, and include any assay to measure or assess proliferation, differentiation, cytokine secretion, cytotoxic activity and/or expression of one or more activation marker. In some embodiments, the simultaneous or near simultaneous binding of such a SLC34A2-binding polypeptide to both of its targets, SLC34A2 expressed on target cell and a T cell molecule expressed on a T cell, e.g. activating T cell antigen, can result in a temporary interaction between the target cell and T cell, thereby resulting in activation, e.g. cytotoxic activity, of the T cell and subsequent lysis of the target cell.

[0208] In some embodiments, the T surface molecule, such as activating T cell antigen, is CD3 or is CD2. Specifically, a provided bispecific SLC34A2-binding polypeptide is capable of specifically binding an activating T cell antigen expressed on a human T cell, such as human CD3 or human CD3. In particular aspects, the additional binding domain that is specific to the activating T cell antigen (e.g. CD3 or CD2) is an antibody or antigen-binding fragment. [0209] Among bispecific antibody T cell-engagers are bispecific T cell engager (BiTE) molecules, which contain tandem scFv molecules fused by a flexible linker (see e.g. Nagorsen and Bauerle, Exp Cell Res 317, 1255-1260 (2011); tandem scFv molecules fused to each other via, e.g. a flexible linker, and that further contain an Fc domain composed of a first and a second subunit capable of stable association (WO2013026837); diabodies and derivatives thereof, including tandem diabodies (Holliger et al, Prot Eng 9, 299-305 (1996); Kipriyanov et al, J Mol Biol 293, 41-66 (1999)); dual affinity retargeting (DART) molecules that can include the diabody format with a C-terminal disulfide bridge; or triomabs that include whole hybrid mouse/rat IgG molecules (Seimetz et al, Cancer Treat Rev 36, 458-467 (2010). Similar formats of any of the above molecules can be generated using any of the anti-SEC34A2 antibodies or antigen binding fragments provided herein.

[0210] In some embodiments, the additional binding domain specific to an activating T cell antigen is an antigen-binding fragment selected from a Fab fragment, a F(ab')2 fragment, an Fv fragment, a scFv, disulfide stabilized Fv fragment (dsFv), a scAb, a dAb, a single domain heavy chain antibody (VHH), or a single domain light chain antibody. In some embodiments, the additional binding domain is monovalent for binding the activating T cell antigen, such as CD2 or CD3.

[0211] In some embodiments, the additional binding domain is capable of binding to CD3 or a CD3 complex. A CD3 complex is a complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor. The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (also referred to as subunits). In some embodiments, the additional binding molecule is an antibody or antigenbinding fragment capable of specifically binding to CD3 or a CD3 complex, also called a CD3- binding domain. In some embodiments, the CD3-binding domain capable of binding CD3 or a CD3 complex includes one or more copies of an anti-CD3 Fab fragment, an anti-CD3 F(ab')2 fragment, an anti-CD3 Fv fragment, an anti-CD3 scFv, an anti-CD3 dsFv, an anti-CD3 scAb, an anti-CD3 dAb, an anti-CD3 single domain heavy chain antibody (VHH), and an anti-CD3 single domain light chain antibody. In some embodiments, the anti-CD3 binding domain is monovalent for binding CD3.

[0212] In some cases, the CD3-binding domain recognizes the CD3s-chain. In some embodiments, the anti-CD3s binding domain includes one or more copies of an anti-CD3s Fab fragment, an anti-CD3s F(ab')2 fragment, an anti-CD3s Fv fragment, an anti-CD3s scFv, an anti- CD3s dsFv, an anti-CD3s scAb, an anti-CD3s dAb, an anti-CD3s single domain heavy chain antibody (VHH), and an anti-CD3s single domain light chain antibody. In some embodiments, the anti-CD3s binding domain is monovalent for binding CD3s.

[0213] Exemplary monoclonal antibodies against CD3 or a CD3 complex include, but are not limited to, OKT3, SP34, UCHT1 or 64.1, or an antigen-binding fragment thereof (See e.g., June, et al., J. Immunol. 136:3945-3952 (1986); Yang, et al., J. Immunol. 137:1097-1100 (1986); and Hayward, et al., Immunol. 64:87-92 (1988)). In some aspects, clustering of CD3 on T cells, e.g., by immobilized or cell-localized or tethered anti-CD3-antibodies, leads to T cell activation similar to the engagement of the T cell receptor but independent from its clone typical specificity. In one embodiment, the CD3-binding domain monovalently and specifically binds a CD3 antigen, and is derived from OKT3 (ORTHOCLONE-OKT3™ (muromonab-CD3); humanized OKT3 (U.S. Pat. No. 7,635,475 and published international application No. W02005040220); SP34 (Pessano et al. The EMBO Journal. 4: 337-344, 1985); humanized variant of SP34 (W02015001085); Teplizumab™ (MGA031, Eli Lilly); an anti-CD3 binding molecule described in US2011/0275787; UCHT1 (Pollard et al. 1987 J Histochem Cytochem. 35(11): 1329-38; W02000041474); NI0401 (W02007/033230); visilizumab (U.S. Pat. No. 5,834,597); BC-3 (Anasetti et al., Transplantation 54: 844 (1992); H2C (described in PCT publication no. W02008/119567); V9 (described in Rodrigues et al., Int J Cancer Suppl 7, 45-50 (1992) and U.S. Pat. No. 6,054,297)). Other anti-CD3 antibodies also can be used in the constructs provided herein, including any described in International published PCT application Nos. WO199404679, W02008119567, WO2015095392, WO2016204966, WO2019133761; published patent application Nos. US20170369563, US20180194842, US20180355038; U.S. Pat. Nos. 7,728,114, 7,381,803, 7,994,289.

[0214] In some embodiments, the SLC34A2-binding polypeptide is a bispecific construct that is or comprises at least one anti-SLC34A2 antibody or antigen binding fragment provided herein and at least one additional binding molecule capable of binding to a surface molecule expressed on a Natural Killer (NK) cells and/or recruiting NK cells. In particular aspects, the multispecific antibody is bispecific for SLC34A2 and the NK cell surface molecule. In some embodiments, the surface molecule is CD 16 (FcyRIII).

[0215] CD 16, a low affinity receptor for the Fc portion of some IgGs known to be involved in antibody-dependent cellular cytotoxicity (ADCC), is the best-characterized membrane receptor responsible for triggering of target cell lysis by NK cells (Mandelboim et al., 1999, PNAS 96:5640-5644). Generally, a large majority (approximately 90%) of human NK cells express CD56 at low density (CD56dim) and FcyRIII (CD16) at a high level (Cooper et al., 2001, Trends Immunol. 22:633-640). Human FcyRIII exists as two isoforms, CD16a (FcyRIIIA) and CD16b (FcyRIIIB), that share 96% sequence identity in their extracellular immunoglobulin-binding regions (van de Winkel and Capel, 1993, Immunol. Today 14(5):215-221). In particular embodiments, the additional binding molecule is capable of specifically binding CD 16a. On NK cells, the alpha chain of CD16a associates with the immunoreceptor tyrosine-based activation motif (IT AM) containing FcsRI y-chain and/or the T-cell receptor (TCR)/CD3^-chain to mediate signaling (Wirthmueller et al., 1992, J. Exp. Med. 175:1381-1390). Engagement of CD16a can result in activating of NK cells expressing CD 16a, thereby eliciting a biological response to trigger cell killing of target cells in a manner analogous to antibody-dependent cellular cytotoxicity (ADCC). For example, a binding molecule that specifically binds SLC34A2 expressed on a tumor cell may target NK-cells to the tumor cell. In some cases, activation of the NK cell caused by the binding molecule binding to CD 16a can lead to killing of the tumor cells.

[0216] In some embodiments, the additional binding domain specific to an activating NK cell receptor, such as CD16a, is an antigen-binding fragment selected from a Fab fragment, a F(ab')2 fragment, an Fv fragment, a scFv, disulfide stabilized Fv fragment (dsFv), a scAb, a dAb, a single domain heavy chain antibody (VHH), or a single domain light chain antibody. In some embodiments, the additional binding domain is monovalent for binding the activating T NK cell receptor, such as CD 16a. Antibodies and antigen-binding fragments thereof specific for CD 16a are known and include, for example, NM3E2 (McCall et al. (1999) Mol. Immunol., 36:433-045. Other anti-CD16a antibodies also can be used in the constructs provided herein, including any described in published U.S. patent application Ser. No. 10/160,280,795; U.S. Pat. No. 9,701,750; Behar et al. (2008) Protein Eng Des Sei. 21:1-10; Arndt et al., (1999) Blood 94:2562-2568. In particular examples, the anti-CD16a is an anti-CD16a scFv. In some embodiments, the anti- CD16a is an anti-CD16a antibody included in a TandAb molecule (see e.g. Reush et al. (2014) Mabs, 6:727-738). In some aspects, the anti-CD16a is an anti-CD16a or antigen binding fragment, such as an scFv, described in U.S. Pat. No. 9,035,026. Single domain antibodies, including VHH domains that bind to CD16a are known, see e.g. published U.S. patent application No. US20160280795. Synthetic Transcriptional Modulator Receptors

[0217] Provided herein are SLC34A2-binding synthetic transcriptional modulator receptors that contain an anti-SCL34A2 antibody or antigen-binding fragment provided herein. In some embodiments, the synthetic transcriptional modulator can activate transcription of a selected gene or genes following binding to a target antigen (e.g., SLC34A2). In various embodiments, the intracellular domain of the synthetic transcriptional modulator receptor is cleaved from the transmembrane domain upon binding of the synthetic transcriptional modulator to SLC34A2. The intracellular domain is then capable of translocating into a cell nucleus where it induces expression of a gene of interest. In some embodiments, the intracellular domain is a transcriptional effector. Exemplary synthetic transcriptional modulator receptors are described in WO2023064928A2 and WO2023225059A2, each of which is incorporated by referenced herein in its entirety and for all purposes.

[0218] The recombinant synthetic transcriptional receptor may be a synthetic human transcriptional modulator, comprising fully human sequences, e.g., natural human sequences. In various embodiments, the synthetic transcriptional modulator comprises (a) an extracellular antigen-binding domain, (b) a transmembrane domain, and (c) an intracellular domain comprising a human or humanized transcriptional effector.

C. Engineered Cells and Chimeric Antigen Receptor

[0219] Provided herein are SLC34A2-binding chimeric antigen receptors (CARs) that contain an anti-SLC34A2 antibody or antigen-binding fragment provided herein. In some embodiments, the SLC34A2-directed CAR generally contains an extracellular antigen-binding domain that includes the antibodies (e.g., antigen-binding antibody fragments), and/or other binding peptides that specifically recognize, such as specifically bind to SLC34A2, such as to SLC34A2 proteins, such as human SLC34A2 protein. In some embodiments, the SLC34A2-binding CAR generally contains an extracellular binding domain and an intracellular signaling domain. In some embodiments, SLC34A2-binding CAR binds to an extracellular region of SLC34A2. In some embodiments, the SLC34A2-binding CAR binds to human SLC34A2 protein comprising the amino acid sequence of SEQ ID NO: 111 (Uniprot 095436), or an allelic variant or splice variant thereof. In some embodiments, the SLC34A2-binding CAR specifically binds to SEQ ID NO: 108. In some embodiments, the SLC34A2-binding CAR specifically binds to SEQ ID NO: 109. In some embodiments, the SLC34A2-binding CAR specifically binds to SEQ ID NO:115.

[0220] In some embodiments, provided herein is a chimeric antigen receptor (CAR) that contains an extracellular antigen-binding domain that includes an any of the provided anti- SLC34A2 antibodies or antigen binding fragments, a transmembrane domain and an intracellular signaling region composed of one or more signaling domains. In particular embodiments, the extracellular antigen binding domain is an scFv comprising a variable heavy chain and a variable light chain of any of the provided antibodies. Also provided herein are engineered cells in which the CAR is expressed on the surface of a cell. [0221] In other embodiments, provided herein are engineered cells that express any of the provided antibodies or antigen-binding fragments or SLC34A2 binding molecules described herein. In particular example, the provided antibodies or antigen binding fragments or SLC34A2 bind molecules thereof are secreted from the cell. In some embodiments, such an antibody or antigen binding fragment or SLC34A2 binding molecule comprises a signal peptide, e.g., an antibody signal peptide or other efficient signal sequence to get domains outside of cell, such as to cause the protein to be secreted by the engineered cell. Generally, the signal peptide, or a portion of the signal peptide, is cleaved from the binding molecule with secretion. The antibody or antigen binding fragment or SLC34A2 binding molecule can be encoded by a nucleic acid (which can be part of an expression vector). In some embodiments, the antibody or antigen binding fragment or a SLC34A2 binding molecule thereof is expressed and secreted by a cell (such as an immune cell, for example a primary immune cell).

[0222] In some embodiments, such provided engineered cells that are engineered to express an antibody or antigen-binding fragment or SLC34A2 binding molecules described herein further contain a chimeric antigen receptor (CARs). In some embodiments, the CAR contains an extracellular domain comprising one or more antigen binding domain specific to SLC34A2. CAR constructs include an extracellular domain containing the one or more extracellular antigen binding domain, a transmembrane domain and an intracellular signaling region. In some cases, the extracellular antigen binding domain is an scFv.

[0223] In general, the extracellular antigen binding domain which form the antigen binding unit of the CAR “binds” or is “capable of binding”, i.e. targets, a target antigen with sufficient affinity such the CAR is useful in therapy in targeting a cell or tissue expressing the target antigen. In some embodiments, the extracellular antigen binding domain can include any of the antibodies or antigen-binding fragments described herein, such as in Section II.

[0224] In provided embodiments, the transmembrane domain of a CAR is a domain that typically crosses or is capable of crossing or spanning the plasma membrane and is connected, directly or indirectly (e.g. via a spacer, such as an immunoglobulin hinge sequence) to the extracellular antigen binding domain and the endoplasmic portion containing the intracellular signaling domain. In one embodiment, the transmembrane domain of the CAR is a transmembrane region of a transmembrane protein (for example Type I transmembrane proteins), an artificial hydrophobic sequence or a combination thereof. In one embodiment, the transmembrane domain comprises the CD3zeta domain or CD28 transmembrane domain. In another embodiments, the transmembrane domain comprises a CD8a transmembrane domain. In some embodiments, the CD8a comprises an amino acid sequence at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 190. In some embodiments, the CD8a comprises the amino acid sequence set forth in SEQ ID NO: 190.

[0225] Other transmembrane domains will be apparent to those of skill in the art and may be used in connection with embodiments of a CAR provided herein.

[0226] In provided embodiments, the intracellular signaling region of a CAR provided herein contains one or more intracellular signaling domain that transmits a signal to a T cell upon engagement of the antigen binding domain of the CAR, such as upon binding antigen. In some embodiments, the intracellular region contains an intracellular signaling domain that is or contains an IT AM signaling domain. Exemplary intracellular signaling domains include, for example, a signaling domain derived from , chain of the T-cell receptor complex or any of its homologs (e.g., q chain, FcsRIy and P chains, MB 1 (Iga) chain, B29 (Ig) chain, etc.), human CD3zeta chain, CD3 polypeptides (A, 5 and a), syk family tyrosine kinases (Syk, ZAP 70, etc.), src family tyrosine kinases (Lek, Fyn, Lyn, etc.), FcRp, FcRy, CDS, CD22, CD79a, CD79b, CD66d, and other molecules involved in T-cell transduction, such as CD2, CD5, 0X40 and CD28. In particular embodiments, the intracellular signaling region contains an intracellular signaling domain derived from the human CD3 zeta chain. In some embodiments, the CD3zeta chain comprises an amino acid sequence at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 192. In some embodiments, the CD3zeta chain comprises the amino acid sequence set forth in SEQ ID NO: 192.

[0227] In some embodiments, the intracellular signaling region of a CAR can further contain an intracellular signaling domain derived from a costimulatory molecule. In such examples, such a signaling domain may enhance CAR-T cell activity, such as via enhancement of proliferation, survival and/or development of memory cells, after antigen specific engagement, for example, compared to a CAR that only contains an IT AM containing signaling domain, e.g. CD3 zeta. In some embodiments, the co-stimulatory domain is a functional signaling domain obtained from a protein selected from: CD28, CD137 (4-1BB), CD134 (0X40), DaplO, CD27, CD2, CD5, ICAM-1, LFA-1 (CD1 la/CD18), Lek, TNFR-I, TNFR-II, Fas, CD30, CD40, CD278 (ICOS) or combinations thereof. In particular embodiments, the costimulatory signaling domain is derived or obtained from a human protein. In some aspects, the costimulatory signaling domain is derived or obtained from human CD28 or human CD137 (4-1BB). In some embodiments, the costimulatory signaling domain is CD28. In some embodiments, the costimulatory signaling domain is 4-1BB (Accession No. Q07011.1). In some embodiments, the 4-1BB comprises an amino acid sequence at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 191. In some embodiments, the 4-1BB comprises the amino acid sequence set forth in SEQ ID NO: 191.

[0228] In particular embodiments, the CAR further comprises a hinge or spacer region which connects the extracellular antigen binding domain and the transmembrane domain. This hinge or spacer region can be used to achieve different lengths and flexibility of the resulting CAR. Examples of the hinge or spacer region that can be used include, but are not limited to, Fc fragments of antibodies or fragments or derivatives thereof, hinge regions of antibodies, or fragments or derivatives thereof, CH2 regions of antibodies, CH3 regions of antibodies, artificial spacer sequences, for example peptide sequences, or combinations thereof. Other hinge or spacer region will be apparent to those of skill in the art and may be used. In one embodiment, the hinge is an lgG4 hinge or a CD8a hinge. In some embodiments, the CD8a hinge comprises an amino acid sequence at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 189. In some embodiments, the CD8a hinge comprises the amino acid sequence set forth in SEQ ID NO: 189.

[0229] In some embodiments, it is understood the CAR may include any sequence that exhibits some sequence variation to any of the above or below described SEQ ID NOS, such as at least 85%, 90%, 95% or more sequence identity thereto. Exemplary sequences of CAR components are provided in Table 6.

Table 6

[0230] Also provided is an isolated cell or cell population that has been genetically modified to express an anti-SLC34A2 antibody or antigen binding fragment a CAR provided herein. In one embodiment, the cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), a regulatory T cell, hematopoietic stem cells and/or pluripotent embryonic/induced stem cells. In some cases, the cell is a T cell, such as a CD4 and/or CD8 T cell. In some embodiments, the cells are autologous to the subject. For example, in some embodiments, T cells may be isolated from a patient (also called primary T cells) for engineering, e.g. transfection or transduction, with a CAR nucleic acid construct.

[0231] In an exemplary example, primary T-cells can be purified ex vivo (CD4 cells or CD8 cells or both) and stimulated with a TCR/CD28 agonists, such as anti-CD3/anti-CD28 coated beads. After a 2 or 3 day activation process, a recombinant expression vector encoding the antibody or binding molecule and/or CAR can be stably introduced into the primary T cells through standard lentiviral or retroviral transduction protocols or plasmid electroporation strategies. Cells can be monitored for secretion of an antibody or SLC34A2 binding molecule and/or CAR expression by, for example, flow cytometry using anti-epitope tag or antibodies that cross-react with native parental molecule.

[0232] The antibody or SLC34A2 binding molecule and/or CAR engineered T-cells can be assayed for appropriate function by a variety of means. In some cases, in vitro cytotoxicity, proliferation, or cytokine assays (e.g., IFN-gamma expression) can be used to assess the function of engineered T-cells. Exemplary standard endpoints are percent lysis of a tumor line, proliferation of the engineered T-cell, or IFN-gamma protein expression in culture supernatant. In some cases, the ability to stimulate activation of T cells upon stimulation of the CAR, e.g. via antigen, can be assessed, such as by monitoring expression of activation markers such as CD69, CD44, or CD62L, proliferation and/or cytokine production.

[0233] Also provided herein are methods for the prevention and/or treatment of a disease or condition in a subject, such as a cancer, that includes administering to a subject engineered cells provided herein. Generally, the subject is in need of treatment for the disease or condition, pharmaceutically active amount of a cell and/or of a pharmaceutical composition of the invention.

D. Nucleic Acids and Expression Vectors and Methods of Producing Antibodies

[0234] The present disclosure provides a nucleic acid or nucleic acids encoding an antibody or antigen-binding fragment thereof. The nucleic acid(s) of the present disclosure may comprise a polynucleotide sequence encoding any one of the anti-SLC34A2 antibodies or antigen-binding fragments thereof disclosed herein. The polypeptide sequences may be used to determine appropriate nucleic acid sequences encoding the particular antibody disclosed thereby. The nucleic acid sequence may be optimized to reflect particular codon "preferences" for various expression systems according to standard methods well known to those of skill in the art.

[0235] Among the provided nucleic acid molecules are those that comprise polynucleotides that encode one or more polypeptides e.g., an immunoglobulin heavy chain or light chain) of a provided anti-SLC34A2 antibody. In some embodiments, a nucleic acid molecule comprises a polynucleotide that encodes a heavy chain or a light chain of an anti-SLC34A2 antibody. In some embodiments, a nucleic acid molecule comprises both a polynucleotide that encodes a heavy chain and a polynucleotide that encodes a light chain of an anti-SLC34A2 antibody. In some embodiments, a first nucleic acid molecule comprises a first polynucleotide that encodes a heavy chain and a second nucleic acid molecule comprises a second polynucleotide that encodes a light chain. Also provided herein are nucleic acid molecules comprising polynucleotides that encode one or more polypeptides of a binding molecule containing any of the provided anti-SLC34A2 antibodies, such as a SLC34A2-targeted antibody-drug conjugate (ADC) or a bispecific immune cell engager comprising the anti-SLC34A2 antibody or antigen binding fragment thereof as described herein.

[0236] In some embodiments, the light chain variable (VL) of the anti-SLC34A2 antibody provided herein is encoded by a nucleic acid molecule comprising a polynucleotide set forth in any one of SEQ ID NOS: 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150 and 152, or a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence set forth in any one of SEQ ID NOS: 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150 and 152; and the heavy chain variable (VH) of the anti-SLC34A2 antibody provided herein is encoded by a nucleic acid molecule comprising a polynucleotide set forth in any one of SEQ ID NOS: 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151 and 153, or a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence set forth in any one of SEQ ID NOS: 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151 and 153.

[0237] In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 122, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 123. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 124, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 125. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 126, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 127. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 128, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 129. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 130, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 131. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 132, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 133. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 134, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 135. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 136, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 137. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 138, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 139. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 140, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 141. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 142, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 143. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 144, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 145. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 146, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 147. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 148, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 149. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 150, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 151. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 152, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 153.

[0238] In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 122, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 123. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 124, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 125. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 126, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 127. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 128, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 129. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 130, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide that set forth in SEQ ID NO: 131. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 132, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 133. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 134, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 135. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 136, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 137. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 138, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 139. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 140, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 141. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 142, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 143. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 144, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 145. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 146, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 147. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 148, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 149. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 150, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 151. In some embodiments, the VL region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 152, and the VH region is encoded by a nucleic acid molecule comprising a polynucleotide set forth in SEQ ID NO: 153. In some embodiments, the nucleic acid(s) is an isolated nucleic acid(s). The polynucleotides may include those encompassing natural and/or non-naturally occurring nucleotides and bases, e.g., including those with backbone modifications. The terms “nucleic acid molecule”, “nucleic acid”, “sequence of nucleotides”, and “polynucleotide” may be used interchangeably, and refer to a polymer of nucleotides. Such polymers of nucleotides may contain natural and/or non-natural nucleotides, and include, but are not limited to, DNA, RNA, and PNA. “Nucleic acid sequence” refers to the linear sequence of nucleotides that comprise the nucleic acid molecule or polynucleotide.

[0239] In some such embodiments, the heavy chain and the light chain are expressed from one nucleic acid molecule, or from two separate nucleic acid molecules, as two separate polypeptides. In some embodiments, such as when an antibody is an scFv, a single polynucleotide encodes a single polypeptide comprising both a heavy chain variable domain fragment and a light chain variable domain fragment linked together. [0240] This disclosure is not intended to be limited with regard to the source of the antibody or the manner in which it is made. Various procedures known within the art may be used for the production of monoclonal antibodies directed against SLC34A2 (See, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, incorporated herein by reference). In some embodiments, the anti-SLC34A2 antibodies, and antigen binding fragments thereof, are recombinantly expressed and produced.

[0241] In some embodiments, a nucleic acid of the present disclosure may be operably linked to a transcriptional control element, e.g., a promoter, and enhancer, etc. Suitable promoter and enhancer elements are known to those of skill in the art.

[0242] In some embodiments, a polynucleotide encoding a heavy chain or light chain of an anti-SLC34A2 antibody comprises a nucleotide sequence that encodes a leader sequence, which, when translated, is located at the N terminus of the heavy chain or light chain. The leader sequence may be the native heavy or light chain leader sequence, or may be another heterologous leader sequence.

[0243] Nucleic acid molecules may be constructed using conventional recombinant DNA techniques well-known in the art. In some embodiments, a nucleic acid molecule is an expression vector that is suitable for expression in a selected host cell.

[0244] Vectors comprising polynucleotides that encode anti-SLC34A2 heavy chains and/or anti-SLC34A2 light chains are provided herein. Vectors comprising polynucleotides that encode anti-SLC34A2 heavy chains and/or anti-SLC34A2 light chains are also provided herein. In certain embodiments, the vector is selected from the group consisting of a DNA vector, an RNA vector, a plasmid, a lentiviral vector, an adenoviral vector, an adeno-associated viral vector, and a retroviral vector. In certain embodiments, the vector is an expression vector. A nucleic acid of the present disclosure may be present within an expression vector and/or a cloning vector. An expression vector can include a selectable marker, an origin of replication, and other features that provide for replication and/or maintenance of the vector. Suitable expression vectors include, e.g., plasmids, viral vectors, and the like. Large numbers of suitable vectors and promoters are known to those of skill in the art; many are commercially available for generating a subject recombinant construct. The following vectors are provided by way of example and should not be construed in anyway as limiting: Bacterial: pBs, phagescript, PsiX174, pBluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene, La Jolla, Calif., USA); pTrc99A, pKK223-3, pKK233-3, pDR540, and pRIT5 (Pharmacia, Uppsala, Sweden). Eukaryotic: pWLneo, pSV2cat, pOG44, PXR1, pSG (Stratagene) pSVK3, pBPV, pMSG and pSVL (Pharmacia). [0245] Expression vectors generally have convenient restriction sites located near the promoter sequence to provide for the insertion of nucleic acid sequences encoding heterologous proteins. A selectable marker operative in the expression host may be present. Suitable expression vectors include, but are not limited to, viral vectors (e.g. viral vectors based on vaccinia virus; poliovirus; adenovirus (see, e.g., Li et al., Invest. Opthalmol. Vis. Sci. (1994) 35: 2543-2549; Borras et al., Gene Ther. (1999) 6: 515-524; Li and Davidson, Proc. Natl. Acad. Sci. USA (1995) 92: 7700-7704; Sakamoto et al., H. Gene Ther. (1999) 5: 1088-1097; WO 94/12649, WO 93/03769; WO 93/19191; WO 94/28938; WO 95/11984 and WO 95/00655); adeno-associated virus (see, e.g., Ali et al., Hum. Gene Ther. (1998) 9: 81-86, Elannery et al., Proc. Natl. Acad. Sci. USA (1997) 94: 6916-6921; Bennett et al., Invest. Opthalmol. Vis. Sci. (1997) 38: 2857-2863; Jomary et al., Gene Ther. (1997) 4:683 690, Rolling et al., Hum. Gene Ther. (1999) 10: 641-648; Ali et al., Hum. Mol. Genet. (1996) 5: 591-594; Srivastava in WO 93/09239, Samulski et al., J. Vir. (1989) 63: 3822-3828; Mendelson et al., Virol. (1988) 166: 154-165; and Llotte et al., Proc. Natl. Acad. Sci. USA (1993) 90: 10613-10617); SV40; herpes simplex virus; human immunodeficiency virus (see, e.g., Miyoshi et al., Proc. Natl. Acad. Sci. USA (1997) 94: 10319- 23; Takahashi et al., J. Virol. (1999) 73: 7812-7816); a retroviral vector (e.g., Murine Leukemia Virus, spleen necrosis virus, and vectors derived from retroviruses such as Rous Sarcoma Virus, Harvey Sarcoma Virus, avian leukosis virus, human immunodeficiency virus, myeloproliferative sarcoma virus, and mammary tumor virus); and the like.

[0246] Additional expression vectors suitable for use are, e.g., without limitation, a lentivirus vector, a gamma retrovirus vector, a foamy virus vector, an adeno-associated virus vector, an adenovirus vector, a pox virus vector, a herpes virus vector, an engineered hybrid virus vector, a transposon mediated vector, and the like. Viral vector technology is well known in the art and is described, for example, in Sambrook et al., 2012, Molecular Cloning: A Laboratory Manual, volumes 1-4, Cold Spring Harbor Press, NY), and in other virology and molecular biology manuals. Viruses, which are useful as vectors include, but are not limited to, retroviruses, adenoviruses, adeno- associated viruses, herpes viruses, and lentiviruses.

[0247] In general, a suitable vector contains an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers, (e.g., WO 01/96584; WO 01/29058; and U.S. Pat. No. 6,326,193).

[0248] In some embodiments, a vector comprises a first polynucleotide sequence encoding a heavy chain and a second polynucleotide sequence encoding a light chain. In some embodiments, the heavy chain and light chain are expressed from the vector as two separate polypeptides. In some embodiments, the heavy chain variable domain fragment and light chain variable domain fragment are expressed as part of a single polypeptide, such as, for example, when the antibody is an scFv.

[0249] In some embodiments, a first vector comprises a polynucleotide that encodes a heavy chain and a second vector comprises a polynucleotide that encodes a light chain. In some embodiments, the first vector and second vector are transfected into host cells in similar amounts (such as similar molar amounts or similar mass amounts). In some embodiments, a mole- or mass-ratio of between 5:1 and 1:5 of the first vector and the second vector is transfected into host cells. In some embodiments, a mass ratio of between 1:1 and 1:5 for the vector encoding the heavy chain and the vector encoding the light chain is used. In some embodiments, a mass ratio of 1:2 for the vector encoding the heavy chain and the vector encoding the light chain is used.

[0250] Also provided is a host cell comprising any of the vectors or nucleic acids disclosed herein. The host cell may be of eukaryotic, prokaryotic, mammalian, or bacterial origin. In various embodiments, anti-SLC34A2 heavy chains and/or anti-SLC34A2 light chains may be expressed in prokaryotic cells, such as bacterial cells; or in eukaryotic cells, such as fungal cells (such as yeast), plant cells, insect cells, and mammalian cells. Such expression may be carried out, for example, according to procedures known in the art. Exemplary eukaryotic cells that may be used to express polypeptides include, but are not limited to, COS cells, including COS 7 cells; HEK293 cells, including HEK293-6E cells; CHO cells, including CHO-S, DG44. Lecl3 CHO cells, and FUT8 CHO cells; PER.C6® cells (Crucell); and NSO cells. In some embodiments, anti- SLC34A2 heavy chains and/or anti-SLC34A2 light chains may be expressed in yeast. See, e.g., U.S. Publication No. US 2006/0270045 Al. In some embodiments, a particular eukaryotic host cell is selected based on its ability to make desired post-translational modifications to the anti- SLC34A2 heavy chains and/or anti-SLC34A2 light chains. For example, in some embodiments, CHO cells produce polypeptides that have a higher level of sialylation than the same polypeptide produced in HEK293 cells.

[0251] Introduction of one or more nucleic acids into a desired host cell may be accomplished by any method, including but not limited to, calcium phosphate transfection, DEAE-dextran mediated transfection, cationic lipid-mediated transfection, electroporation, transduction, infection, etc. Nonlimiting exemplary methods are described, e.g., in Sambrook el al., Molecular Cloning, A Laboratory Manual, 3^rd ed. Cold Spring Harbor Laboratory Press (2001). Nucleic acids may be transiently or stably transfected in the desired host cells, according to any suitable method. [0252] Also provided herein are host cells comprising any of the polynucleotides or vectors described herein. In some embodiments host cells are capable of over-expressing heterologous DNAs can be used for the purpose of isolating the genes encoding the antibody, polypeptide or protein of interest. Non-limiting examples of mammalian host cells include but not limited to COS, HeLa, and CHO cells. See also PCT Publication No. WO 87/04462. Suitable nonmammalian host cells include prokaryotes (such as E. coli or B. subtilis) and yeast (such as .S'. cerevisiae, S. pombe; or K. laclis).

[0253] A method of producing an antibody or antigen-binding fragment thereof that binds to SLC34A2 is also provided herein, wherein the method comprises culturing the host cell. In some embodiments, the nucleic acids encoding a subject antibody are introduced directly into a host cell, and the cell incubated under conditions sufficient to induce expression of the encoded antibody. Expression may conveniently be achieved by culturing under appropriate conditions recombinant host cells containing the nucleic acid. Following production by expression, an antibody or antigen-binding fragment thereof, may be isolated and/or purified using any suitable technique, and then used as desired.

[0254] Anti-SLC34A2 antibodies may be purified by any suitable method. Such methods include, but are not limited to, the use of affinity matrices or hydrophobic interaction chromatography. Suitable affinity ligands such as ligands that bind antibody constant regions. For example, a Protein A, Protein G, Protein A/G, or an antibody affinity column may be used to bind the constant region and to purify an anti-SEC34A2 antibody. Hydrophobic interactive chromatography, for example, a butyl or phenyl column, may also be suitable for purifying some polypeptides such as antibodies. Ion exchange chromatography (e.g., anion exchange chromatography and/or cation exchange chromatography) may also be suitable for purifying some polypeptides such as antibodies. Mixed- mode chromatography (e.g., reversed phase/anion exchange, reversed phase/cation exchange, hydrophilic interaction/anion exchange, hydrophilic interaction/cation exchange, etc.) may also be suitable for purifying some polypeptides such as antibodies. Many methods of purifying polypeptides are known in the art.

[0255] Antibodies or antigen-binding fragments thereof as provided herein, and encoding nucleic acid molecules and vectors, may be isolated and/or purified, e.g. from their natural environment, in substantially pure or homogeneous form, or, in the case of nucleic acid, free or substantially free of nucleic acid or genes of origin other than the sequence encoding a polypeptide with the desired function. IV. PHARMACEUTICAL COMPOSITIONS

[0256] Provided herein are compositions containing any of the provided antibodies or antigen-binding fragments or binding molecules containing same as described herein. The pharmaceutical composition can further comprise a pharmaceutically acceptable excipient. For example, the pharmaceutical composition can contain one or more excipients for modifying, maintaining or preserving, for example, the pH, osmolarity, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption, or penetration of the composition. Such compositions may comprise buffers such as neutral buffered saline, phosphate buffered saline and the like; carbohydrates such as glucose, mannose, sucrose or dextrans, mannitol; proteins; polypeptides or amino acids such as glycine; antioxidants; chelating agents such as EDTA or glutathione; adjuvants (e.g., aluminum hydroxide); and preservatives.

[0257] In some embodiments, the pharmaceutical composition is a solid, such as a powder, capsule, or tablet. For example, the components of the pharmaceutical composition can be lyophilized. In some embodiments, the solid pharmaceutical composition is reconstituted or dissolved in a liquid prior to administration.

[0258] In some embodiments, the pharmaceutical composition is a liquid, for example a provided protein dissolved in an aqueous solution (such as physiological saline or Ringer’s solution). In some embodiments, the pH of the pharmaceutical composition is between about 4.0 and about 8.5 (such as between about 4.0 and about 5.0, between about 4.5 and about 5.5, between about 5.0 and about 6.0, between about 5.5 and about 6.5, between about 6.0 and about 7.0, between about 6.5 and about 7.5, between about 7.0 and about 8.0, or between about 7.5 and about 8.5).

[0259] In some embodiments, the pharmaceutical composition comprises a pharmaceutically- acceptable excipient, for example a filler, binder, coating, preservative, lubricant, flavoring agent, sweetening agent, coloring agent, a solvent, a buffering agent, a chelating agent, or stabilizer. Examples of pharmaceutically-acceptable fillers include cellulose, dibasic calcium phosphate, calcium carbonate, microcrystalline cellulose, sucrose, lactose, glucose, mannitol, sorbitol, maltol, pregelatinized starch, com starch, or potato starch. Examples of pharmaceutically- acceptable binders include polyvinylpyrrolidone, starch, lactose, xylitol, sorbitol, maltitol, gelatin, sucrose, polyethylene glycol, methyl cellulose, or cellulose. Examples of pharmaceutically-acceptable coatings include hydroxypropyl methylcellulose (HPMC), shellac, com protein zein, or gelatin. Examples of pharmaceutically-acceptable disintegrants include polyvinylpyrrolidone, carboxymethyl cellulose, or sodium starch glycolate. Examples of pharmaceutically-acceptable lubricants include polyethylene glycol, magnesium stearate, or stearic acid. Examples of pharmaceutically-acceptable preservatives include methyl parabens, ethyl parabens, propyl paraben, benzoic acid, or sorbic acid. Examples of pharmaceutically- acceptable sweetening agents include sucrose, saccharine, aspartame, or sorbitol. Examples of pharmaceutically-acceptable buffering agents include carbonates, citrates, gluconates, acetates, phosphates, or tartrates.

[0260] In some embodiments, the pharmaceutical composition further comprises an agent for the controlled or sustained release of the product, such as injectable microspheres, bio-erodible particles, polymeric compounds (polylactic acid, polyglycolic acid), beads, or liposomes.

[0261] In some embodiments, the pharmaceutical composition is sterile. Sterilization may be accomplished by filtration through sterile filtration membranes or radiation. Where the composition is lyophilized, sterilization using this method may be conducted either prior to or following lyophilization and reconstitution. The composition for parenteral administration may be stored in lyophilized form or in solution. In addition, parenteral compositions generally are placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle.

[0262] A pharmaceutically acceptable carrier may be a pharmaceutically acceptable material, composition, or vehicle. For example, the carrier may be a liquid or solid filler, diluent, excipient, solvent, or encapsulating material, or some combination thereof. Each component of the carrier must be “pharmaceutically acceptable” in that it must be compatible with the other ingredients of the formulation. It also must be suitable for contact with any tissue, organ, or portion of the body that it may encounter, meaning that it must not carry a risk of toxicity, irritation, allergic response, immunogenicity, or any other complication that excessively outweighs its therapeutic benefits.

[0263] In some embodiments, the pharmaceutical composition is for administration to a subject. Generally, dosages and routes of administration of the pharmaceutical composition are determined according to the size and condition of the subject, according to standard pharmaceutical practice. For example, the therapeutically effective dose can be estimated initially either in cell culture assays or in animal models such as mice, rats, rabbits, dogs, pigs, or monkeys. An animal model may also be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans. The exact dosage will be determined in light of factors related to the subject requiring treatment. Dosage and administration are adjusted to provide sufficient levels of the active compound or to maintain the desired effect. Factors that may be taken into account include the severity of the disease state, the general health of the subject, the age, weight, and gender of the subject, time and frequency of administration, drug combination(s), reaction sensitivities, and response to therapy.

[0264] Long-acting pharmaceutical compositions may be administered every 3 to 4 days, every week, or biweekly depending on the half-life and clearance rate of the particular formulation. The frequency of dosing will depend upon the pharmacokinetic parameters of the molecule in the formulation used. Typically, a composition is administered until a dosage is reached that achieves the desired effect. The composition may therefore be administered as a single dose, or as multiple doses (at the same or different concentrations/dosages) over time, or as a continuous infusion. Further refinement of the appropriate dosage is routinely made. Appropriate dosages may be ascertained through use of appropriate dose-response data.

[0265] In some embodiments, the pharmaceutical composition is for administration to a subject through any route, including orally, transdermally, by inhalation, intravenously, intraarterially, intramuscularly, direct application to a wound site, application to a surgical site, intraperitoneally, by suppository, subcutaneously, intradermally, transcutaneously, by nebulization, intrapleurally, intraventricularly, intra-articularly, intraocularly, or intraspinally.

[0266] A provided pharmaceutical formulation may, for example, be in a form suitable for intravenous infusion.

[0267] In some embodiments, the dosage of the pharmaceutical composition is a single dose or a repeated dose. In some embodiments, the doses are given to a subject once per day, twice per day, three times per day, or four or more times per day. In some embodiments, about 1 or more (such as about 2 or more, about 3 or more, about 4 or more, about 5 or more, about 6 or more, or about 7 or more) doses are given in a week. In some embodiments, multiple doses are given over the course of days, weeks, months, or years. In some embodiments, a course of treatment is about 1 or more doses (such as about 2 or more does, about 3 or more doses, about 4 or more doses, about 5 or more doses, about 7 or more doses, about 10 or more doses, about 15 or more doses, about 25 or more doses, about 40 or more doses, about 50 or more doses, or about 100 or more doses).

[0268] In some embodiments, an administered dose of the pharmaceutical composition is about 1 pg of protein per kg subject body mass or more (such as about 2 pg of protein per kg subject body mass or more, about 5 pg of protein per kg subject body mass or more, about 10 pg of protein per kg subject body mass or more, about 25 pg of protein per kg subject body mass or more, about 50 pg of protein per kg subject body mass or more, about 100 pg of protein per kg subject body mass or more, about 250 pg of protein per kg subject body mass or more, about 500 pg of protein per kg subject body mass or more, about 1 mg of protein per kg subject body mass or more, about 2 mg of protein per kg subject body mass or more, or about 5 mg of protein per kg subject body mass or more).

V. METHODS OF USE

[0269] The antibodies and antigen-binding fragments or SLC34A2 binding molecules containing the same described herein, including pharmaceutical compositions thereof, can be used in a variety of therapeutic applications, such as the treatment of a disease. Such methods and uses include therapeutic methods and uses, for example, involving administration of the molecules or compositions containing the same, to a subject having a disease or disorder. In some embodiments, the molecule or engineered cell is administered in an effective amount to effect treatment of the disease or disorder. Uses include uses of the antibodies and antigen-binding fragments or SLC34A2 binding molecules containing the same described herein, including pharmaceutical compositions thereof, in such methods and treatments, and in the preparation of a medicament in order to carry out such therapeutic methods. In some embodiments, the methods are carried out by administering the antibodies and antigen-binding fragments or SLC34A2 binding molecules containing the same, including pharmaceutical compositions thereof, or compositions comprising the same, to the subject having or suspected of having the disease or disorder. In some embodiments, the methods thereby treat the disease or disorder in the subject. Also provided are any methods or uses involving administering a provided engineered cell as described, or pharmaceutical compositions containing the same, for treating a disease or disorder.

[0270] Illustrative subjects include mammalian subjects, such as farm animals, domestic animals, and human patients. In particular embodiments, the subject is a human subject. The terms subject and patient are used interchangeably herein.

[0271] In some cases, a subject is selected that is known, suspected or that has been identified as having a tumor expressing SLC34A2. A provided antibody or antigen-binding fragment, SLC34A2 binding molecule or engineered cell as described herein, or pharmaceutical composition comprising the same, is administered to the subject. The administration to the subject will generally have an effect due to its binding with the SLC34A2 target.

[0272] Generally, alleviation or treatment of a disease or disorder involves the lessening of one or more symptoms or medical problems associated with the disease or disorder. For example, in the case of cancer, the therapeutically effective amount of the drug can accomplish one or a combination of the following: reduce the number of cancer cells; reduce the tumor size; inhibit (i.e., to decrease to some extent and/or stop) cancer cell infiltration into peripheral organs; inhibit tumor metastasis; inhibit, to some extent, tumor growth; and/or relieve to some extent one or more of the symptoms associated with the cancer. In some embodiments, a composition of this disclosure can be used to prevent the onset or reoccurrence of the disease or disorder in the subject.

[0273] In some embodiments, the antibody or antigen-binding fragment, SLC34A2 binding molecule or engineered cell as described herein, or pharmaceutical composition comprising the same, can be used to inhibit growth of mammalian cancer cells (such as human cancer cells). A method of treating cancer can include administering an effective amount of any of the pharmaceutical compositions described herein to a subject with cancer. The effective amount of the pharmaceutical composition can be administered to inhibit, halt, or reverse progression of cancers. Human cancer cells can be treated in vivo, or ex vivo. In ex vivo treatment of a human patient, tissue or fluids containing cancer cells are treated outside the body and then the tissue or fluids are reintroduced back into the patient. In some embodiments, the cancer is treated in a human patient in vivo by administration of the therapeutic composition into the patient.

[0274] In some embodiments, the antibody or antigen-binding fragment, SLC34A2 binding molecule or engineered cell as described herein, or pharmaceutical composition comprising the same, are useful in treating, alleviating a symptom of, ameliorating and/or delaying the progression of a disease or disorder. In some embodiments, the disease or disorder is a cancer, tumor or other neoplastic condition. In some embodiments, the cancer is bladder cancer, breast cancer, gastric cancer, uterine/cervical cancer, ovarian cancer, prostate cancer, testicular cancer, esophageal cancer, gastrointestinal cancer, pancreatic cancer, colorectal cancer, colon cancer, kidney cancer, head and neck cancer, lung cancer, stomach cancer, germ cell cancer, bone cancer, liver cancer, thyroid cancer, skin cancer, neoplasm of the central nervous system, lymphoma, leukemia, myeloma, sarcoma, and virus-related cancer. In some embodiments, the cancer is ovarian cancer. In certain embodiments, the cancer is a metastatic cancer, refractory cancer, or recurrent cancer.

[0275] Compositions of the invention can be administered in dosages and routes and at times to be determined in appropriate pre-clinical and clinical experimentation and trials. Compositions may be administered multiple times at dosages within these ranges. Administration of the compositions may be combined with other methods useful to treat the desired disease or condition as determined by those of skill in the art. Typically, precise amount of the compositions of the present disclosure to be administered can be determined by a physician with consideration of individual differences in age, weight, tumor size, extent of infection or metastasis, and condition of the patient (subject).

[0276] In some embodiments, a therapeutically effective dose may be, by way of nonlimiting example, from about 0.01 pg/kg body weight to about 10 mg/kg body weight. In some embodiments, the therapeutically effective dose may be, by way of nonlimiting example, from about 0.01 mg/kg body weight to about 5-10 mg/kg body weight. Common dosing frequencies may range, for example, from twice daily to once a week.

[0277] In some embodiments, a therapeutic amount of an engineered cell composition of the present disclosure is administered. It can generally be stated that a pharmaceutical composition comprising engineered cells, e.g., T cells, as described herein may be administered at a dosage of 10⁴ to 10⁹ cells/kg body weight, such as 10⁵ to 10⁶ cells/kg body weight, including all integer values within those ranges. Engineered cell compositions, such as T cell compositions, may also be administered multiple times at these dosages. The cells can be administered by using infusion techniques that are commonly known in immunotherapy (see, e.g., Rosenberg et al, New Eng. J. of Med. 319: 1676, 1988). The optimal dosage and treatment regime for a particular patient can readily be determined by one skilled in the art of medicine by monitoring the patient for signs of disease and adjusting the treatment accordingly.

[0278] The antibody or antigen-binding fragment, SLC34A2 binding molecule or engineered cell, or pharmaceutical composition comprising the same, of the present disclosure can be administered alone or in combination with other modes of treatment, such as other anti-cancer agents. They can be provided before, substantially contemporaneous with, or after other modes of treatment (i.e., concurrently or sequentially). In some embodiments, the method of treatment described herein can further include administering: radiation therapy, chemotherapy, vaccination, targeted tumor therapy, CAR-T therapy, oncolytic virus therapy, cancer immunotherapy, cytokine therapy, surgical resection, chromatin modification, ablation, cryotherapy, an antisense agent against a tumor target, a siRNA agent against a tumor target, a microRNA agent against a tumor target or an anti-cancer/tumor agent, or a biologic, such as an antibody, cytokine, or receptor extracellular domain-Fc fusion. VI. ARTICLES OF MANUFACTURE OR KITS

[0279] Provided herein are articles of manufacture and kits comprising the provided compositions In some embodiments, the kit comprises any of the provided compositions and instructions for administering the composition to a subject.

[0280] Kits can optionally include one or more components such as instructions for use, devices and additional reagents (e.g., sterilized water or saline solutions for dilution of the compositions and/or reconstitution of lyophilized protein), and components, such as tubes, containers and syringes for practice of the methods. In some embodiments, the kits can further contain reagents for collection of samples, preparation and processing of samples, and/or reagents for quantitating the amount of one or more surface markers in a sample, such as, but not limited to, detection reagents, such as antibodies, buffers, substrates for enzymatic staining, chromagens or other materials, such as slides, containers, microtiter plates, and optionally, instructions for performing the methods. Those of skill in the art will recognize many other possible containers and plates and reagents that can be used in accord with the provided methods.

[0281] In some embodiments, the kits can be provided as articles of manufacture that include packing materials for the packaging of the cells, antibodies or reagents, or compositions thereof, or one or more other components. For example, the kits can contain containers, bottles, tubes, vial and any packaging material suitable for separating or organizing the components of the kit. The one or more containers may be formed from a variety of materials such as glass or plastic. In some embodiments, the one or more containers hold a composition comprising cells or an antibody or other reagents for use in the methods. The article of manufacture or kit herein may comprise the cells, antibodies or reagents in separate containers or in the same container.

[0282] In some embodiments, the one or more containers holding the composition may be a single-use vial or a multi-use vial, which, in some cases, may allow for repeat use of the composition. In some embodiments, the article of manufacture or kit may further comprise a second container comprising a suitable diluent. The article of manufacture or kit may further include other materials desirable from a commercial, therapeutic, and user standpoint, including other buffers, diluents, filters, needles, syringes, therapeutic agents and/or package inserts with instructions for use.

[0283] In some embodiments, the kit can, optionally, include instructions. Instructions typically include a tangible expression describing the cell composition, reagents and/or antibodies and, optionally, other components included in the kit, and methods for using such. In some embodiments, the instructions indicate methods for using the cell compositions and antibodies for administration to a subject for treating a disease or condition, such as in accord with any of the provided embodiments. In some embodiments, the instructions are provided as a label or a package insert, which is on or associated with the container. In some embodiments, the instructions may indicate directions for reconstitution and/or use of the composition.

VII. EXEMPLARY EMBODIMENTS

[0284] Among the provided embodiments are:

Embodiment 1. An antibody or antigen-binding fragment thereof that binds Solute Carrier Family 34 Member 2 (SLC34A2), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein

(i) the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) each having a sequence that is contained within SEQ ID NO:1 or SEQ ID NO: 161, and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) each having a sequence that is contained within SEQ ID NO:5 or SEQ ID NO: 162; (ii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:9 or SEQ ID NO: 163, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 13 or SEQ ID NO: 164; (iii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 15 or SEQ ID NO: 165, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 19 or SEQ ID NO: 154; (iv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:23 or SEQ ID NO: 166, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:27 or SEQ ID NO: 167; (v) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:31 or SEQ ID NO: 168, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:35 or SEQ ID NO: 155;

(vi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:39 or SEQ ID NO: 169, and the VL region comprises a CDR- Ll, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:43

I ll or SEQ ID NO: 156; (vii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:47 or SEQ ID NO: 170, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:51 or SEQ ID NO: 171; (viii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:53 or SEQ ID NO: 172, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:56 or SEQ ID NO: 173; (ix) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:59 or SEQ ID NO: 174, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:63 or SEQ ID NO:157; (x) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:66 or SEQ ID NO: 175, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:70 or SEQ ID NO: 158; (xi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:73 or SEQ ID NO: 176, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:76 or SEQ ID NO: 177; (xii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:78 or SEQ ID NO: 178, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:82 or SEQ ID NO: 179;

(xiii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:84 or SEQ ID NO: 180, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:88 or SEQ ID NO: 181; (xiv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR- H3 each having a sequence that is contained within SEQ ID NO:90 or SEQ ID NO: 182, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:93 or SEQ ID NO: 183; (xv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO:94 or SEQ ID NO: 184, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO:97 or SEQ ID NO: 159; (xvi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 100 or SEQ ID NO: 185, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 103 or SEQ ID NO: 160.

Embodiment 2. The antibody or antigen-binding fragment thereof of embodiment 1, wherein each CDR is defined in accordance with the Kabat definition, the Chothia definition, the combination of the Kabat and the Chothia definition, the AbM definition, or the contact definition.

Embodiment 3. An antibody or antigen-binding fragment thereof that specifically binds Solute Carrier Family 34 Member 2 (SLC34A2), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein: (i) the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) comprising the sequences set forth in SEQ ID NOS: 2, 3, and 4, respectively, and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) comprising the sequences set forth in SEQ ID NOS: 6, 7, and 8, respectively; (ii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 11, and 12, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7 and 14, respectively; (iii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 16, 17 and 18, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 20, 21 and 22, respectively; (iv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 24, 25 and 26, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 28, 29 and 30, respectively; (v) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 32, 33 and 34, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 37 and 38, respectively; (vi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 40, 41 and 42, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 44, 45 and 46, respectively; (vii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 48, 49 and 50, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 186 and 52, respectively; (viii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 48, 54 and 55, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 57 and 58, respectively; (ix) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 60, 61 and 62, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 64, 21 and 65, respectively; (x) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 67, 68 and 69, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 28, 71 and 72, respectively; (xi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 32, 74 and 75, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 187, 186 and 77, respectively; (xii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 79, 80 and 81, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 186 and 83, respectively; (xiii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 85, 86 and 87, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 89, 21 and 65, respectively; (xiv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 91 and 92, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7 and 8, respectively; (xv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR- H3 comprising the sequences set forth in SEQ ID NOS: 95, 3 and 96, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 98 and 99, respectively; or (xvi) the VH region comprises a CDR-H1, a CDR- H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 101, 102 and 96, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 187, 104 and 105, respectively.

Embodiment 4. The antibody or antigen-binding fragment thereof of any of embodiments 1 to 3, wherein: (i) the VH region comprises an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 161, and the VL region comprises an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 5 or SEQ ID NO: 162; (ii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 9 or SEQ ID NO: 163, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 13 or SEQ ID NO: 164; (iii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 15 or SEQ ID NO: 165, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 19 or SEQ ID NO: 154; (iv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 23 or SEQ ID NO: 166, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 27 or SEQ ID NO: 167; (v) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 31 or SEQ ID NO: 168, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 35 or SEQ ID NO: 155; (vi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 39 or SEQ ID NO: 169, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 43 or SEQ ID NO: 156; (vii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 47 or SEQ ID NO: 170, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 51 or SEQ ID NO: 171; (viii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 53 or SEQ ID NO: 172, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 56 or SEQ ID NO: 173; (ix) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 59 or SEQ ID NO: 174, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 63 or SEQ ID NO: 157; (x) the V_H region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 66 or SEQ ID NO: 175, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 70 or SEQ ID NO: 15; (xi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 73 or SEQ ID NO: 176, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 76 or SEQ ID NO: 177; (xii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 78 or SEQ ID NO: 178, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 82 or SEQ ID NO: 179; (xiii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 84 or SEQ ID NO: 180, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 88 or SEQ ID NO: 181; (xiv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 90 or SEQ ID NO: 182, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 93 or SEQ ID NO: 183; (xv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 94 or SEQ ID NO: 184, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 97 or SEQ ID NO: 159; (xvi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 100 or SEQ ID NO: 185, and the V_L region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 103 or SEQ ID NO: 160.

Embodiment 5. An antibody or antigen-binding fragment thereof that specifically binds Solute Carrier Family 34 Member 2 (SLC34A2), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein: (i) the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) comprising the sequences set forth in SEQ ID NOS: 2, 3, and 4, respectively, and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) comprising the sequences set forth in SEQ ID NOS: 6, 7, and 8, respectively; (ii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 11, and 12, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7 and 14, respectively; (iii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 16, 17 and 18, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 20, 21 and 22, respectively; (iv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 24, 25 and 26, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 28, 29 and 30, respectively; (v) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 32, 33 and 34, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 37 and 38, respectively; (vi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 40, 41 and 42, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 44, 45 and 46, respectively; (vii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 48, 49 and 50, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 186 and 52, respectively; (viii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 48, 54 and 55, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 57 and 58, respectively; (ix) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 60, 61 and 62, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 64, 21 and 65, respectively; (x) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 67, 68 and 69, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 28, 71 and 72, respectively; (xi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 32, 74 and 75, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 187, 186 and 77, respectively; (xii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 79, 80 and 81, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 186 and 83, respectively; (xiii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 85, 86 and 87, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 89, 21 and 65, respectively; (xiv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 91 and 92, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7 and 8, respectively; (xv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR- H3 comprising the sequences set forth in SEQ ID NOS: 95, 3 and 96, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 98 and 99, respectively; or (xvi) the VH region comprises a CDR-H1, a CDR- H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 101, 102 and 96, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 187, 104 and 105, respectively.

Embodiment 6. The antibody or antigen-binding fragment thereof of any of embodiments 1 to 5, wherein: (i) the VH region comprises an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 161, and the VL region comprises an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 5 or SEQ ID NO: 162; (ii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 9 or SEQ ID NO: 163, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 13 or SEQ ID NO: 164; (iii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 15 or SEQ ID NO: 165, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 19 or SEQ ID NO: 154; (iv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 23 or SEQ ID NO: 166, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 27 or SEQ ID NO: 167; (v) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 31 or SEQ ID NO: 168, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 35 or SEQ ID NO: 155; (vi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 39 or SEQ ID NO: 169, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 43 or SEQ ID NO: 156; (vii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 47 or SEQ ID NO: 170, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 51 or SEQ ID NO: 171; (viii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 53 or SEQ ID NO: 172, and the V_L region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 56 or SEQ ID NO: 173; (ix) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 59 or SEQ ID NO: 174, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 63 or SEQ ID NO: 157; (x) the V_H region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 66 or SEQ ID NO: 175, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 70 or SEQ ID NO: 158; (xi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 73 or SEQ ID NO: 176, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 76 or SEQ ID NO: 177; (xii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 78 or SEQ ID NO: 178, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 82 or SEQ ID NO: 179; (xiii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 84 or SEQ ID NO: 180, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 88 or SEQ ID NO: 181; (xiv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 90 or SEQ ID NO: 182, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 93 or SEQ ID NO: 183; (xv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 94 or SEQ ID NO: 184, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 97 or SEQ ID NO: 159; or (xvi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 100 or SEQ ID NO: 185, and the V_L region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 103 or SEQ ID NO: 160.

Embodiment 7. The antibody or antigen-binding fragment thereof of any of embodiments 1 to 6, wherein: (i) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 1 or 161 and 5 or 162, respectively; (ii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 9 or 163 and 13 or 164, respectively; (iii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 15 or 165 and 19 or 154, respectively; (iv) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 23 or 166 and 27 or 167, respectively; (v) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 31 or 168 and 35 or 155, respectively; (vi) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 39 or 169 and 43 or 156, respectively; (vii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 47 or 170 and 51 or 171, respectively;

(viii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 53 or 172 and 56 or 173, respectively; (ix) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 59 or 174 and 63 or 157, respectively; (x) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 66 or 175 and 70 or 158, respectively; (xi) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 73 or 176 and 76 or 177, respectively; (xii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 78 or 178 and 82 or 179, respectively; (xiii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 84 or 180 and 88 or 181, respectively; (xiv) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 90 or 182 and 93 or 183, respectively; (xv) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 94 or 184 and 97 or 159, respectively; or (xvi) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 100 or 185 and 103 or 160, respectively

Embodiment 8. The antibody or antigen-binding fragment thereof of any of embodiments 1 to 7, wherein the antibody is a full-length antibody. Embodiment 9. The antibody or antigen-binding fragment thereof of any of embodiments 1 to 8, wherein the heavy chain further comprises a constant domain of a human immunoglobulin heavy chain and the light chain further comprises a constant domain of a human light chain. Embodiment 10. The antibody or antigen-binding fragment thereof of any of embodiments 1 to

9, wherein the constant domain of a human immunoglobulin heavy chain is from a IgGl heavy chain.

Embodiment 11. The antibody or antigen-binding fragment thereof of any of embodiments 1 to

10, wherein the constant domain of a human immunoglobulin heavy chain comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO:113.

Embodiment 12. The antibody or antigen-binding fragment thereof of any of embodiments 1 to

11, wherein the constant domain of a human immunoglobulin heavy chain comprises the amino acid sequence of SEQ ID NO: 113.

Embodiment 13. The antibody or antigen-binding fragment thereof of any of embodiments 1 to

12, wherein the constant domain of a human light chain is from a human kappa light chain. Embodiment 14. The antibody or antigen-binding fragment thereof of any of embodiments 1 to

13, wherein the constant domain of a human light chain comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 114.

Embodiment 15. The antibody or antigen-binding fragment thereof of any of embodiments 1 to

14, wherein the constant domain of a human light chain comprises the amino acid sequence of SEQ ID NO: 114.

Embodiment 16. The antibody or antigen-binding fragment thereof of any of embodiments 1 to

15, wherein the full-length antibody comprises a heavy chain constant domain comprising the amino acid sequence of SEQ ID NO: 113, and a light chain constant domain comprising the amino acid sequence of SEQ ID NO: 114.

Embodiment 17. The antibody or antigen-binding fragment thereof of any of embodiments 1 to 7, wherein the antibody is an antigen-binding fragment.

Embodiment 18. The antibody or antigen-binding fragment thereof of any of embodiments 1 to 7 and 17, wherein the antigen-binding fragment is a Fab. Embodiment 19. The antibody or antigen-binding fragment thereof of any of embodiments 1 to 7 and 17, wherein the antigen-binding fragment thereof comprises a single chain variable fragment (scFv).

Embodiment 20. The antibody or antigen-binding fragment thereof of embodiment 19, wherein the VH is amino-terminal to VL.

Embodiment 21. The antibody or antigen-binding fragment thereof of embodiment 19, wherein the VH is carboxy-terminal to VL.

Embodiment 22. The antibody or antigen-binding fragment thereof of any of embodiments 1 to

21, wherein the antibody or antigen-binding fragment thereof is monoclonal.

Embodiment 23. The antibody or antigen-binding fragment thereof of any of embodiments 1 to

22, wherein the antibody or antigen-binding fragment thereof is recombinant.

Embodiment 24. The antibody or antigen-binding fragment thereof of any of embodiments 1 to

23, wherein the VH and VL are human or are derived from a human protein.

Embodiment 25. The antibody or antigen-binding fragment thereof of any of embodiments 1 to

24, wherein the antibody or antigen-binding fragment thereof specifically binds to a human SLC34A2 protein.

Embodiment 26. The antibody or antigen-binding fragment thereof of embodiment 25, wherein the human SLC34A2 protein is set forth by the amino acid sequence of SEQ ID NO: 108.

Embodiment 27. The antibody or antigen-binding fragment thereof of embodiment 25, wherein the human SLC34A2 protein is set forth by the amino acid sequence of SEQ ID NO: 111.

Embodiment 28. The antibody or antigen-binding fragment thereof of embodiment 25, wherein the human SLC34A2 protein is set forth by the amino acid sequence of SEQ ID NO: 115.

Embodiment 29. The antibody or antigen-binding fragment thereof of any of embodiments 1 to 28, wherein the EC50 value of binding to human SLC34A2 protein is in the range of about 5 to 50 nM.

Embodiment 30. The antibody or antigen-binding fragment thereof of embodiment 29, wherein the EC50 value is less than 15 nM.

Embodiment 31. The antibody or antigen-binding fragment thereof of embodiment 29 or embodiment 30, wherein the EC50 value is based on binding to SLC34A2 expressed on OVCAR3 cells.

Embodiment 32. A conjugate, comprising the SLC34A2 antibody or antigen-binding fragment thereof of any one of embodiments 1 to 31, and a heterologous moiety. Embodiment 33. A synthetic receptor, comprising an extracellular antigen-binding domain comprising the antibody or antigen-binding fragment thereof of any of embodiments 1 to 31. Embodiment 34. The synthetic receptor of embodiment 33, wherein the synthetic receptor is a chimeric antigen receptor (CAR) further comprising a spacer, transmembrane domain, and an intracellular signaling domain.

Embodiment 35. A chimeric antigen receptor (CAR), comprising an extracellular antigenbinding domain comprising an antibody or antigen-binding fragment thereof of any of embodiments 1 to 31, a spacer, transmembrane domain, and an intracellular signaling domain.

Embodiment 36. A synthetic receptor comprising from N-terminus to C-terminus an extracellular antigen-binding domain comprising the antibody or antigen-binding fragment of any of embodiments 1 to 31, a transmembrane domain, and an intracellular domain comprising transcriptional effector.

Embodiment 37. The synthetic receptor of embodiment 36, wherein the intracellular domain is a human or humanized transcriptional effector.

Embodiment 38. A nucleic acid molecule(s) encoding the heavy chain and/or the light chain of the antibody or antigen-binding fragment thereof of any of embodiments 1 to 31.

Embodiment 39. A vector comprising the nucleic acid of embodiment 38.

Embodiment 40. The vector of embodiment 39, wherein the vector is an expression vector.

Embodiment 41. A host cell comprising the nucleic acid of embodiment 38 or the vector of embodiment 39 or embodiment 40.

Embodiment 42. The host cell of embodiment 41, which is a mammalian cell.

Embodiment 43. A method of producing an antibody or antigen-binding fragment thereof comprising culturing the host cell of embodiment 41 or embodiment 42 under a condition that produces the antibody or antigen-binding fragment thereof.

Embodiment 44. The method of embodiment 43, further comprising recovering the antibody or antigen-binding fragment thereof produced by the host cell

Embodiment 45. An antibody or antigen-binding fragment thereof produced by the method of embodiment 43 or embodiment 44.

Embodiment 46. A composition comprising the antibody or antigen-binding fragment thereof of any one of embodiments 1 to 31, the conjugate of embodiment 32, the synthetic receptor of embodiment 33 or embodiment 34, the CAR of embodiment 35, or the synthetic receptor of embodiment 36 or embodiment 37. Embodiment 47. The composition of embodiment 44, that is a pharmaceutical composition further comprising a pharmaceutically acceptable excipient.

Embodiment 48. A method of treatment, comprising administering the antibody or antigenbinding fragment thereof of any one of embodiments 1 to 31, the conjugate of embodiment 32, the synthetic receptor of embodiment 33 or embodiment 34, the CAR of embodiment 35, or the synthetic receptor of embodiment 36 or embodiment 37, or the composition of embodiment 46 or embodiment 47, to a subject having a disease or disorder.

Embodiment 49. The method of embodiment 48, wherein the disease or disorder is a cancer, optionally ovarian cancer.

Embodiment 50. The method of embodiment 48 or embodiment 49, wherein the subject is a human.

Embodiment 51. Use of a composition of embodiment 46 or embodiment 47 for the manufacture of a medicament for treatment of a disease or disorder.

Embodiment 52. Use of a composition of embodiment 46 or embodiment 47 for treatment of a disease or disorder.

Embodiment 53. The use of embodiment 51 or embodiment 52, wherein the disease or disorder is a cancer, optionally ovarian cancer.

Embodiment 54. A composition of embodiment 46 or embodiment 47 for use in treatment of a disease or disorder.

Embodiment 55. The composition of embodiment 54, wherein the disease or disorder is a cancer, optionally ovarian cancer.

VIII. EXAMPLES

[0285] The following examples are included for illustrative purposes only and are not intended to limit the scope of the invention.

Example 1: Generation and Assessment of SLC34A2 Antibodies

[0286] This example provides methods used to generate human anti-Solute Carrier Family 34 Member 2 (SLC34A2) monoclonal antibodies.

[0287] Human SLC34A2 (alias: NPT2B) is a multi-pass transmembrane protein of the solute carrier family with annotated 8 transmembrane regions according to Uniprot (entry 095436 • NPT2B_HUMAN). Structure predictions identified the longest extracellular loop (herein called ECL2), set forth in SEQ ID NO: 109 and corresponding to residues 234-362 within human SLC34A2 protein, as the optimal target region for raising antibodies. SLC34A2 extracellular loop ( ECL2; SEQ ID NO: 109)

VEVATHYLEIITQLIVESFHFKNGEDAPDLLKVITKPFTKLIVQLDKKVISQIAMNDEK AKNKSEVKIWCKTFTNKTOINVTVPSTANCTSPSLCWTDGIQNWTMKNVTYKENI AKCQHIFVNFHEPDE

A. Immunization Strategies

[0288] Human antibodies that bind to SEC34A2 were generated by immunizing mice that were genetically modified to produce antibodies containing fully human antibody variable regions with three different antigen approaches.

[0289] The goal of the three different antigen approaches was to generate optimal antibody diversity towards human SEC34A2. Specifically, the mice were immunized with one of the following immunogens:

(i) an SEC34A2-KEH conjugate composed of a SEC34A2 peptide fragment (underlined and bold amino acids in ECE2 sequence, corresponding to amino acids 79-106 of ECE2 sequence set forth in SEQ ID NO: 109) with a C-terminal Cysteine residue (SEQ ID NO: 106), which served as an acceptor for conjugation to KLH (Q10583.2; SEQ ID NO: 107);

(ii) an SLC34A2 recombinant fusion protein (SEQ ID NO: 108) composed of the human SLC34A2 ECL2 sequence (SEQ ID NO: 109) fused to a murine Fc domain (SEQ ID NO: 110);

(iii) cells expressing SLC34A2, namely EpH4 cells, which are a murine breast cancer cell line modified to overexpress full-length human SLC34A2 (SEQ ID NO: 111).

[0290] Mice were injected up to 9 times intraperitoneally, subcutaneously, or in the hock. The mice immunized with peptide (i) or cells (iii) were given a priming dose of human SLC34A2 DNA (NM_006424; SEQ ID NO: 112) linked to gold particles that was administered using a gene gun. The spleen and lymph nodes of serum-titer positive mice were harvested and antibodies specific to human SLC34A2 were generated using single B cell cloning.

B. Single B Cell Cloning and Antibody Sequencing

[0291] Single B cell cloning (SBC) was used to isolate SLC34A2-specific monoclonal antibodies from the immunized mice described above. The lymph nodes and/or spleen cells were incubated and stained using markers identifying live and dead cells, markers identifying IgG- positive class- switched memory B-cells, as well as two or more soluble SLC34A2 antigens (SLC34A2 peptide set forth in SEQ ID NO: 115 and/or SLC34A2 recombinant fusion protein set forth in SEQ ID NO: 108). [0292] Using a FACS sorter, antigen- specific B cells were individually sorted at 1 cell per well into multi- well plates containing lysis buffer, thereby lysing the cells and releasing the RNA. Lysates were subjected to multiple rounds of PCR to isolate the VH and VL regions of the captured B cell receptor for next generation sequencing (NGS) and to append promoter/signal peptide and constant region blocks to the requisite ends of the variable region.

[0293] The final PCR reactions generated Transcriptionally Active PCR (TAP) (Liang et al., J Biol Chem. 2002: 277 (5): 3593-8) products that were transfected via high-throughput methods into Expi293 cells and purified using protein A to generate small-scale amounts of recombinant hlgGl/kappa antibody (SEQ ID NOS: 113 and 114) material for screening by ELISA and flow cytometry.

[0294] The VH and VL regions from the positive human SLC34A2 monoclonal antibodies were recovered and sequenced by NGS.

C. Binding to SLC34A2 positive cells

[0295] Antibodies were screened by standard flow cytometry methods for binding to human OVCAR-3 human ovarian cancer cells which endogenously express human SLC34A2. HEK293 cells were used as a non-transfected negative control. Briefly, OVCAR-3 and HEK293 cells that had been detached were incubated at 4°C for 30-60 minutes with 8 serial dilutions of the SLC34A2 antibody (eight 5-fold dilution steps, starting from a top concentration of 133nM Ab). Cells were washed before adding fluorescently labelled anti-human Fc secondary antibody (AF647 F(ab')2 gt-anti-hu IgG Fc-specific; Jackson Cat No 109-606-098) for at least 30 minutes at 4°C. Stained cells were then resuspended in cold FACS buffer and analyzed by flow cytometry for geometric mean fluorescent intensity (GeoMFI) and total cell counts on an iQue automated flow cytometer.

[0296] About 262 antibodies that bind specifically to SLC34A2-expressing OVCAR3 and not HEK293 cells were identified. 16 antibodies were chosen for further characterization. The sequences of these 16 SLC34A2 antibodies are shown in Table El below. Table El sets forth the SEQ ID NO corresponding to the sequence for the VH and three HCDRs, and VL and three LCDRs. Alternative VL sequences of the SLC34A2 antibodies provided herein can start with N- terminal amino acid residues “DIQ” in place of “AIR” and are expected to retain binding as described in the present Examples.

Example 2: SLC34A2 Antibody Epitope Binding

[0297] This example provides methods used to determine the epitope recognized by SLC34A2 monoclonal antibodies in Table El of Example 1.

[0298] The epitope recognized by the SLC34A2 antibodies was determined by ELISA binding assays using the SLC34A2 peptide immunogen (SEQ ID NO: 115), the ECL-mFc fusion protein (SEQ ID NO: 108), and a biotinylated irrelevant peptide as negative control. Briefly, NeutrAvidin plates were coated at Ipg/ml overnight, washed and incubated with blocking buffer for at least 1 hr. Biotinylated antigens as well as irrelevant antigens were then added at 1 ug/ml for at least Ihr at RT, followed by rigorous washing. HRP-conjugated anti-human Fc detection reagent (goat anti-human IgG-Fc-HRP cat: 109-036-098; Jackson ImmunoResearch) was applied and incubated at 4°C for 30-60min. After additional wash steps, 3,3',5,5'-Tetramethylbenzidine (TMB) substrate was added and optical density read using an appropriate plate reader.

[0299] The epitope identified for each of the 16 antibodies is shown in Table E2. EC50 values for binding SLC34A2-expressing OVCAR3 cells as determined in Example 1 are also shown in Table E2. Several strong binders with an EC50 less than 15 nM were identified

N.N. means epitope is unknown; mECL2-Fc protein corresponds to SEQ ID NO: 108; peptide 1 corresponds to SEQ ID NO: 115. [0300] The present invention is not intended to be limited in scope to the particular disclosed embodiments, which are provided, for example, to illustrate various aspects of the invention. Various modifications to the compositions and methods described will become apparent from the description and teachings herein. Such variations may be practiced without departing from the true scope and spirit of the disclosure and are intended to fall within the scope of the present disclosure.

Sequences

Claims

Claims WHAT IS CLAIMED:

1. An antibody or antigen-binding fragment thereof that binds Solute Carrier Family 34 Member 2 (SLC34A2), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein

(i) the VH region comprises a heavy chain complementarity determining region 1 (CDR- Hl), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) each having a sequence that is contained within SEQ ID NO: 1 or SEQ ID NO: 161, and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) each having a sequence that is contained within SEQ ID NO :5 or SEQ ID NO: 162;

(ii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 9 or SEQ ID NO: 163, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 13 or SEQ ID NO: 164;

(iii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 15 or SEQ ID NO: 165, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 19 or SEQ ID NO: 154;

(iv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 23 or SEQ ID NO: 166, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 27 or SEQ ID NO: 167;

(v) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 31 or SEQ ID NO: 168, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 35 or SEQ ID NO: 155;

(vi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 39 or SEQ ID NO: 169, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 43 or SEQ ID NO: 156; (vii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 47 or SEQ ID NO: 170, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 51 or SEQ ID NO: 171;

(viii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 53 or SEQ ID NO: 172, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 56 or SEQ ID NO: 173;

(ix) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 59 or SEQ ID NO: 174, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 63 or SEQ ID NO: 157;

(x) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 66 or SEQ ID NO: 175, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 70 or SEQ ID NO: 158;

(xi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 73 or SEQ ID NO: 176, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 76 or SEQ ID NO: 177;

(xii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 78 or SEQ ID NO: 178, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 82 or SEQ ID NO: 179;

(xiii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 84 or SEQ ID NO: 180, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 88 or SEQ ID NO: 181;

(xiv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 90 or SEQ ID NO: 182, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 93 or SEQ ID NO: 183; (xv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 94 or SEQ ID NO: 184, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 97 or SEQ ID NO: 159;

(xvi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 each having a sequence that is contained within SEQ ID NO: 100 or SEQ ID NO: 185, and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 each having a sequence that is contained within SEQ ID NO: 103 or SEQ ID NO: 160.

2. The antibody or antigen-binding fragment thereof of claim 1, wherein each CDR is defined in accordance with the Kabat definition, the Chothia definition, the combination of the Kabat and the Chothia definition, the AbM definition, or the contact definition.

3. An antibody or antigen-binding fragment thereof that specifically binds Solute Carrier Family 34 Member 2 (SLC34A2), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein:

(i) the VH region comprises a heavy chain complementarity determining region 1 (CDR- Hl), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) comprising the sequences set forth in SEQ ID NOS: 2, 3, and 4, respectively, and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) comprising the sequences set forth in SEQ ID NOS: 6, 7, and 8, respectively;

(ii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 11, and 12, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7 and 14, respectively;

(iii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 16, 17 and 18, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 20, 21 and 22, respectively;

(iv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 24, 25 and 26, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 28, 29 and 30, respectively;

(v) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 32, 33 and 34, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 37 and 38, respectively;

(vi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 40, 41 and 42, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 44, 45 and 46, respectively;

(vii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 48, 49 and 50, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 186 and 52, respectively;

(viii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 48, 54 and 55, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 57 and 58, respectively;

(ix) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 60, 61 and 62, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 64, 21 and 65, respectively;

(x) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 67, 68 and 69, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 28, 71 and 72, respectively;

(xi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 32, 74 and 75, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 187, 186 and 77, respectively;

(xii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 79, 80 and 81, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 186 and 83, respectively;

(xiii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 85, 86 and 87, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 89, 21 and 65, respectively;

(xiv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 91 and 92, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7 and 8, respectively;

(xv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 95, 3 and 96, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 98 and 99, respectively; or

(xvi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 101, 102 and 96, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 187, 104 and 105, respectively.

4. The antibody or antigen-binding fragment thereof of any of claims 1 to 3, wherein:

(i) the VH region comprises an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 161, and the VL region comprises an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 5 or SEQ ID NO: 162;

(ii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 163, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 13 or SEQ ID NO: 164;

(iii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 15 or SEQ ID NO: 165, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 19 or SEQ ID NO: 154;

(iv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 23 or SEQ ID NO: 166, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 27 or SEQ ID NO: 167;

(v) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 31 or SEQ ID NO: 168, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 35 or SEQ ID NO: 155;

(vi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 39 or SEQ ID NO: 169, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 43 or SEQ ID NO: 156;

(vii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 47 or SEQ ID NO: 170, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 51 or SEQ ID NO: 171;

(viii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 53 or SEQ ID NO: 172, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 56 or SEQ ID NO: 173;

(ix) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 59 or SEQ ID NO: 174, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 63 or SEQ ID NO: 157; (x) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 66 or SEQ ID NO: 175, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 70 or SEQ ID NO: 15;

(xi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 73 or SEQ ID NO: 176, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 76 or SEQ ID NO: 177;

(xii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 78 or SEQ ID NO: 178, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 82 or SEQ ID NO: 179;

(xiii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 84 or SEQ ID NO: 180, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 88 or SEQ ID NO: 181;

(xiv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 90 or SEQ ID NO: 182, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 93 or SEQ ID NO: 183;

(xv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 94 or SEQ ID NO: 184, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 97 or SEQ ID NO: 159;

(xvi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 100 or SEQ ID NO: 185, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 103 or SEQ ID NO: 160.

5. An antibody or antigen-binding fragment thereof that specifically binds Solute Carrier Family 34 Member 2 (SLC34A2), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein:

(i) the VH region comprises a heavy chain complementarity determining region 1 (CDR- Hl), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) comprising the sequences set forth in SEQ ID NOS: 2, 3, and 4, respectively, and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) comprising the sequences set forth in SEQ ID NOS: 6, 7, and 8, respectively;

(ii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 11, and 12, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7 and 14, respectively;

(iii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 16, 17 and 18, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 20, 21 and 22, respectively;

(iv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 24, 25 and 26, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 28, 29 and 30, respectively;

(v) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 32, 33 and 34, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 37 and 38, respectively;

(vi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 40, 41 and 42, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 44, 45 and 46, respectively; (vii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 48, 49 and 50, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 186 and 52, respectively;

(viii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 48, 54 and 55, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 57 and 58, respectively;

(ix) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 60, 61 and 62, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 64, 21 and 65, respectively;

(x) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 67, 68 and 69, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 28, 71 and 72, respectively;

(xi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 32, 74 and 75, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 187, 186 and 77, respectively;

(xii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 79, 80 and 81, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 186 and 83, respectively;

(xiii) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 85, 86 and 87, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 89, 21 and 65, respectively;

(xiv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 10, 91 and 92, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 6, 7 and 8, respectively; (xv) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 95, 3 and 96, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 36, 98 and 99, respectively; or

(xvi) the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the sequences set forth in SEQ ID NOS: 101, 102 and 96, respectively, and the VL region comprises a CDR-L1, a CDR-L2 and a CDR-L3 comprising the sequences set forth in SEQ ID NOS: 187, 104 and 105, respectively.

6. The antibody or antigen-binding fragment thereof of any of claims 1 to 5, wherein:

(i) the VH region comprises an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 161, and the VL region comprises an amino acid sequence that has at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 5 or SEQ ID NO: 162;

(ii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 163, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 13 or SEQ ID NO: 164;

(iii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 15 or SEQ ID NO: 165, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 19 or SEQ ID NO: 154;

(iv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 23 or SEQ ID NO: 166, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 27 or SEQ ID NO: 167;

(v) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 31 or SEQ ID NO: 168, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 35 or SEQ ID NO: 155;

(vi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 39 or SEQ ID NO: 169, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 43 or SEQ ID NO: 156;

(vii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 47 or SEQ ID NO: 170, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 51 or SEQ ID NO: 171;

(viii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 53 or SEQ ID NO: 172, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 56 or SEQ ID NO: 173;

(ix) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 59 or SEQ ID NO: 174, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 63 or SEQ ID NO: 157;

(x) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 66 or SEQ ID NO: 175, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 70 or SEQ ID NO: 158;

(xi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 73 or SEQ ID NO: 176, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 76 or SEQ ID NO: 177; (xii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 78 or SEQ ID NO: 178, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 82 or SEQ ID NO: 179;

(xiii) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 84 or SEQ ID NO: 180, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 88 or SEQ ID NO: 181;

(xiv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 90 or SEQ ID NO: 182, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 93 or SEQ ID NO: 183;

(xv) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 94 or SEQ ID NO: 184, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 97 or SEQ ID NO: 159; or

(xvi) the VH region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 100 or SEQ ID NO: 185, and the VL region comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 103 or SEQ ID NO: 160.

7. The antibody or antigen-binding fragment thereof of any of claims 1 to 6, wherein:

(i) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 1 or 161 and 5 or 162, respectively;

(ii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 9 or 163 and 13 or 164, respectively;

(iii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 15 or 165 and 19 or 154, respectively; (iv) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 23 or 166 and 27 or 167, respectively;

(v) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 31 or 168 and 35 or 155, respectively;

(vi) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 39 or 169 and 43 or 156, respectively;

(vii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 47 or 170 and 51 or 171, respectively;

(viii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 53 or 172 and 56 or 173, respectively;

(ix) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 59 or 174 and 63 or 157, respectively;

(x) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 66 or 175 and 70 or 158, respectively;

(xi) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 73 or 176 and 76 or 177, respectively;

(xii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 78 or 178 and 82 or 179, respectively;

(xiii) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 84 or 180 and 88 or 181, respectively;

(xiv) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 90 or 182 and 93 or 183, respectively;

(xv) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 94 or 184 and 97 or 159, respectively; or

(xvi) the VH and the VL comprise the sequence set forth in SEQ ID NOS: 100 or 185 and 103 or 160, respectively.

8. The antibody or antigen-binding fragment thereof of any of claims 1 to 7, wherein the antibody is a full-length antibody.

9. The antibody or antigen-binding fragment thereof of any of claims 1 to 8, wherein the heavy chain further comprises a constant domain of a human immunoglobulin heavy chain and the light chain further comprises a constant domain of a human light chain.

10. The antibody or antigen-binding fragment thereof of any of claims 1 to 9, wherein the constant domain of a human immunoglobulin heavy chain is from a IgGl heavy chain.

11. The antibody or antigen-binding fragment thereof of any of claims 1 to 10, wherein the constant domain of a human immunoglobulin heavy chain comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 113.

12. The antibody or antigen-binding fragment thereof of any of claims 1 to 11, wherein the constant domain of a human immunoglobulin heavy chain comprises the amino acid sequence of SEQ ID NO: 113.

13. The antibody or antigen-binding fragment thereof of any of claims 1 to 12, wherein the constant domain of a human light chain is from a human kappa light chain.

14. The antibody or antigen-binding fragment thereof of any of claims 1 to 13, wherein the constant domain of a human light chain comprises an amino acid sequence having at least at or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 114.

15. The antibody or antigen-binding fragment thereof of any of claims 1 to 14, wherein the constant domain of a human light chain comprises the amino acid sequence of SEQ ID NO: 114.

16. The antibody or antigen-binding fragment thereof of any of claims 1 to 15, wherein the full-length antibody comprises a heavy chain constant domain comprising the amino acid sequence of SEQ ID NO: 113, and a light chain constant domain comprising the amino acid sequence of SEQ ID NO: 114.

17. The antibody or antigen-binding fragment thereof of any of claims 1 to 7, wherein the antibody is an antigen-binding fragment.

18. The antibody or antigen-binding fragment thereof of any of claims 1 to 7 and 17, wherein the antigen-binding fragment is a Fab.

19. The antibody or antigen-binding fragment thereof of any of claims 1 to 7 and 17, wherein the antigen-binding fragment thereof comprises a single chain variable fragment (scFv).

20. The antibody or antigen-binding fragment thereof of claim 19, wherein the VH is amino-terminal to VL.

21. The antibody or antigen-binding fragment thereof of claim 19, wherein the VH is carboxy-terminal to VL.

22. The antibody or antigen-binding fragment thereof of any of claims 1 to 21, wherein the antibody or antigen-binding fragment thereof is monoclonal.

23. The antibody or antigen-binding fragment thereof of any of claims 1 to 22, wherein the antibody or antigen-binding fragment thereof is recombinant.

24. The antibody or antigen-binding fragment thereof of any of claims 1 to 23, wherein VH and VL are human or are derived from a human protein.

25. The antibody or antigen-binding fragment thereof of any of claims 1 to 24, wherein the antibody or antigen-binding fragment thereof specifically binds to a human SLC34A2 protein.

26. The antibody or antigen-binding fragment thereof of claim 25, wherein the human SLC34A2 protein is set forth by the amino acid sequence of SEQ ID NO: 108.

27. The antibody or antigen-binding fragment thereof of claim 25, wherein the human SLC34A2 protein is set forth by the amino acid sequence of SEQ ID NO: 111.

28. The antibody or antigen-binding fragment thereof of claim 25, wherein the human SLC34A2 protein is set forth by the amino acid sequence of SEQ ID NO: 115.

29. The antibody or antigen-binding fragment thereof of any of claims 1 to 28, wherein the EC50 value of binding to human SLC34A2 protein is in the range of about 5 to 50 nM.

30. The antibody or antigen-binding fragment thereof of claim 29, wherein the EC50 value is less than 15 nM.

31. The antibody or antigen-binding fragment thereof of claim 29 or claim 30, wherein the EC50 value is based on binding to SLC34A2 expressed on OVCAR3 cells.

32. A conjugate, comprising the SLC34A2 antibody or antigen-binding fragment thereof of any one of claims 1 to 31, and a heterologous moiety.

33. A synthetic receptor, comprising an extracellular antigen-binding domain comprising the antibody or antigen-binding fragment thereof of any of claims 1 to 31.

34. The synthetic receptor of claim 33, wherein the synthetic receptor is a chimeric antigen receptor (CAR) further comprising a spacer, transmembrane domain, and an intracellular signaling domain.

35. A chimeric antigen receptor (CAR), comprising an extracellular antigen-binding domain comprising an antibody or antigen-binding fragment thereof of any of claims 1 to 31, a spacer, transmembrane domain, and an intracellular signaling domain.

36. A synthetic receptor comprising from N-terminus to C-terminus an extracellular antigen-binding domain comprising the antibody or antigen-binding fragment thereof of any of claims 1 to 31, a transmembrane domain, and an intracellular domain comprising a transcriptional effector.

37. The synthetic receptor of claim 36, wherein the intracellular domain is a human or humanized transcriptional effector.

38. A nucleic acid molecule(s) encoding the heavy chain and/or the light chain of the antibody or antigen-binding fragment thereof of any of claims 1 to 31.

39. A vector comprising the nucleic acid of claim 38.

40. The vector of claim 39, wherein the vector is an expression vector.

41. A host cell comprising the nucleic acid of claim 38 or the vector of claim 39 or claim 40.

42. The host cell of claim 41, which is a mammalian cell.

43. A method of producing an antibody or antigen-binding fragment thereof comprising culturing the host cell of claim 41 or claim 42 under a condition that produces the antibody or antigen-binding fragment thereof.

44. The method of claim 43, further comprising recovering the antibody or antigenbinding fragment thereof produced by the host cell

45. An antibody or antigen-binding fragment thereof produced by the method of claim 43 or claim 44.

46. A composition comprising the antibody or antigen-binding fragment thereof of any one of claims 1 to 31, the conjugate of claim 32, the synthetic receptor of claim 33 or claim 34, the CAR of claim 35, or the synthetic receptor of claim 36 or claim 37.

47. The composition of claim 44, that is a pharmaceutical composition further comprising a pharmaceutically acceptable excipient.

48. A method of treatment, comprising administering the antibody or antigen-binding fragment thereof of any one of claims 1 to 31, the conjugate of claim 32, the synthetic receptor of claim 33 or claim 34, the CAR of claim 35, or the synthetic receptor of claim 36 or claim 37, or the composition of claim 46 or claim 47, to a subject having a disease or disorder.

49. The method of claim 48, wherein the disease or disorder is a cancer, optionally ovarian cancer.

50. The method of claim 48 or claim 49, wherein the subject is a human.

51. Use of a composition of claim 46 or claim 47 for the manufacture of a medicament for treatment of a disease or disorder.

52. Use of a composition of claim 46 or claim 47 for treatment of a disease or disorder.

53. The use of claim 51 or claim 52, wherein the disease or disorder is a cancer, optionally ovarian cancer.

54. A composition of claim 46 or claim 47 for use in treatment of a disease or disorder.

55. The composition of claim 54, wherein the disease or disorder is a cancer, optionally ovarian cancer.