WO2024258743A1

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Publication number: WO2024258743A1
Application number: PCT/US2024/033036
Authority: WO
Inventors: Pia Challita-Eid; Sabine G. ROTTMANN; Dong Jun Lee; Andrew M. HAU; Maria SHAHMORADGOLI; Richard H. LI
Original assignee: Adcentrx Therapeutics Inc
Current assignee: Adcentrx Therapeutics Inc
Priority date: 2023-06-13
Filing date: 2024-06-07
Publication date: 2024-12-19
Anticipated expiration: 2025-12-13
Also published as: TW202504637A

Abstract

Antibody drug conjugates (ADCs) that bind to NECTIN-4 protein(s) and variants thereof are described herein. NECTIN-4 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, the ADCs of the invention provide a therapeutic composition for the treatment of cancer.

Description

ADC Schema (III) or

ADC Schema (IV) or a pharmaceutically acceptable salt or solvate thereof, wherein: • Ab is the Antibody unit, e.g., a NECTIN-4 antibody of the present invention; • each R is independently selected from N, CH, or C; • R’ is C or CH • W is selected from:

In some embodiments, the antibody drug conjugate compound has the following formula:

• Ab is the antibody unit, e.g., anti-NECTIN-4 antibody of the present invention. • Each R is independently selected from N, CH, or C. • W is selected from:

• Xb is a spacer moiety selected from the group consisting of an alkyl, a heteroalkyl, polyethylene glycol (PEG), and a peptide. • b is 0, 1 or 2. • Y_b is a polypeptide moiety that comprises about 1 to about 6 amino acids that are natural and/or unnatural amino acids. • Z_b is a self-immolative moiety including but not limited to:

• D is a drug unit having cytostatic or cytotoxic activity against the target cell. • p is an integer from 1 to 20 or alternatively 1-50. In some embodiments, the antibody drug conjugate compound has the following formula:

ADC Schema (VII) or a pharmaceutically acceptable salt or solvate thereof, wherein: • Ab is the unit, e.g., a NECTIN-4 antibody of the present invention; 1

• R is , wherein R² is a unsubstituted or substituted C₁-C₆ alkyl, heteroalkyl, cycloalkyl or cycloheteroalkyl; • each of R^x and R^y is independently selected from R and L-R^z, provided that when one of R^x and R^y is NR^z, the other is R; • R⁵ is H or CR’₃, wherein each R’ is independently H or F; • R⁶ is H or CH₂CN; • LU is a linker unit; and • R is H or a C₁-C₃ alkyl; and • i is an integer in the range of 1 to about 20. In some embodiments, the antibody drug conjugate compound has the following formula:

ADC Schema (VIII) or a pharmaceutically acceptable salt or solvate thereof, wherein: Ab is the Antibody unit, e.g., a NECTIN-4 antibody of the present invention; 1

R is , wherein R² is a unsubstituted or substituted C₁-C₆ alkyl, heteroalkyl, cycloalkyl or cycloheteroalkyl; each of R^x and R^y is independently selected from R and L-R^z, provided that when one of R^x and R^y is NR^z, the other is R; R⁵ is H or CR’₃, wherein each R’ is independently H or F; R⁶ is H or CH₂CN; LU is a linker unit; and R is H or a C₁-C₃ alkyl; and j is an integer in the range of 1 to about 20. In some embodiments, the antibody drug conjugate compound has the following formula:

ADC Schema (IX) or a pharmaceutically acceptable salt or solvate thereof, wherein: Ab is the Antibody unit, e.g., a NECTIN-4 antibody of the present invention; 1

R is , wherein R² is a unsubstituted or substituted C₁-C₆ alkyl, heteroalkyl, cycloalkyl or cycloheteroalkyl; each of R^x and R^y is independently selected from R and L-R^z, provided that when one of R^x and R^y is NR^z, the other is R; R⁵ is H or CR’₃, wherein each R’ is independently H or F; R⁶ is H or CH₂CN; LU is a linker unit; and R is H or a C₁-C₃ alkyl; and k is an integer in the range of 1 to about 20. In some embodiments, the antibody drug conjugate compound has the following formula:

• a or or cycloheteroalkyl; • R³ is H or C₁-C₃ alkyl; • R⁵ is H or CR’₃ wherein each R’ is independently H or F; • R⁶ is H or CH₂CN; • Ab is the antibody unit, e.g., anti-NECTIN-4 antibody of the present invention. • Each R is independently selected from N, CH, or C. • J is a conjugation moiety. • X_b is a spacer moiety selected from the group consisting of an alkyl, a heteroalkyl, polyethylene glycol (PEG), and a peptide. • b is 0, 1 or 2. • Y_b is a polypeptide moiety that comprises about 1 to about 6 amino acids that are natural and/or unnatural amino acids. • Z_b is a self-immolative moiety including but not limited to:

For compositions comprising a plurality of antibodies, the drug loading is represented by p, the average number of drug molecules per Antibody. Drug loading may range from 1 to 24 drugs (D) per Antibody. The average number of drugs per antibody in preparation of conjugation reactions may be characterized by conventional means such as mass spectroscopy, ELISA assay, and HPLC. The quantitative distribution of Antibody-Drug-Conjugates in terms of p may also be determined. In some instances, separation, purification, and characterization of homogeneous Antibody-Drug-conjugates where p is a certain value from Antibody-Drug-Conjugates with other drug loadings may be achieved by means such as reverse phase HPLC or electrophoresis. In exemplary embodiments, p is from 2 to 8. In some embodiments, p is from 2 to 24. The generation of Antibody-drug conjugate compounds can be accomplished by any technique known to the skilled artisan. Briefly, the Antibody-drug conjugate compounds comprise NECTIN-4 antibodies. In one embodiment, the NECTIN-4 ADC comprises the antibody heavy chain sequence set forth in Table VI(A). In another embodiment, the NECTIN-4 ADC comprises the antibody heavy chain sequence set forth in Table VI(B). In another embodiment, the NECTIN-4 ADC comprises the antibody heavy chain sequence set forth in Table VI(C). In another embodiment, the NECTIN-4 ADC comprises the antibody heavy chain sequence set forth in Table VI(D). In another embodiment, the NECTIN-4 ADC comprises the antibody heavy chain sequence set forth in Table VI(E). In another embodiment, the NECTIN-4 ADC comprises the antibody heavy chain sequence set forth in Table VI(F). In another embodiment, the NECTIN-4 ADC comprises the antibody light chain sequence set forth in Table VI(G). In another embodiment, the NECTIN-4 ADC comprises the antibody light chain sequence set forth in Table VI(H). In another embodiment, the NECTIN-4 ADC comprises the antibody light chain sequence set forth in Table VI(I). In another embodiment, the NECTIN-4 ADC comprises the antibody light chain sequence set forth in Table VI(J). In another embodiment, the NECTIN-4 ADC comprises the antibody light chain sequence set forth in Table VI(K). In another embodiment, the NECTIN-4 ADC comprises the antibody light chain sequence set forth in Table VI(L). In another embodiment, the NECTIN-4 ADC comprises the antibody heavy chain variable region sequence(s) set forth in Table VIII. In another embodiment, the NECTIN-4 ADC comprises the antibody light chain variable region sequence(s) set forth in Table IX. In another embodiment, the NECTIN-4 ADC comprises the antibody CDR sequence(s) set forth in Table X. In another embodiment, the aforementioned NECTIN-4 antibodies are conjugated to a therapeutic agent. In one embodiment, the therapeutic agent is a Drug-Linker (DL) payload set forth in Figure 10. In one embodiment, the DL payload is set forth in Figure 10(A) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(B) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(C) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(D) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(E) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(F) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(G) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(H) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(I) and has the following chemical structure: or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(J) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(K) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(L) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(M) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(N) and has the following chemical structure: or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(O) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. In one embodiment, the DL payload is set forth in Figure 10(P) and has the following chemical structure:

or a pharmaceutically acceptable salt or solvate form thereof. A number of different reactions are available for covalent attachment of drugs and/or linkers to binding agents. This is often accomplished by reaction of the amino acid residues of the binding agent, e.g., antibody molecule, including the amine groups of lysine, the free carboxylic acid groups of glutamic and aspartic acid, the sulfhydryl groups of cysteine and the various moieties of the aromatic amino acids. One of the most commonly used non-specific methods of covalent attachment is the carbodiimide reaction to link a carboxy (or amino) group of a compound to amino (or carboxy) groups of the antibody. Additionally, bifunctional agents such as dialdehydes or imidoesters have been used to link the amino group of a compound to amino groups of an antibody molecule. Also available for attachment of drugs to binding agents is the Schiff base reaction. This method involves the periodate oxidation of a drug that contains glycol or hydroxy groups, thus forming an aldehyde which is then reacted with the binding agent. Attachment occurs via formation of a Schiff base with amino groups of the binding agent. Isothiocyanates can also be used as coupling agents for covalently attaching drugs to binding agents. Other techniques are known to the skilled artisan and within the scope of the present invention. In certain embodiments, an intermediate, which is the precursor of the linker, is reacted with the drug under appropriate conditions. In certain embodiments, reactive groups are used on the drug and/or the intermediate. The product of the reaction between the drug and the intermediate, or the derivatized drug, is subsequently reacted with the NECTIN-4 antibodies under appropriate conditions. IV.) Linker Units Typically, the antibody-drug conjugate compounds comprise a Linker unit between the drug unit and the antibody unit. In some embodiments, the linker is cleavable under intracellular conditions, such that cleavage of the linker releases the drug unit from the antibody in the intracellular environment. In yet other embodiments, the linker unit is not cleavable, and the drug is released, for example, by antibody degradation. In a preferred embodiment, the linker is conjugated to a NECTIN-4 antibody described herein. In some embodiments, the linker is cleavable by a cleaving agent that is present in the intracellular environment (e.g., within a lysosome or endosome or caveolea). The linker can be, e.g., a peptidyl linker that is cleaved by an intracellular peptidase or protease enzyme, including, but not limited to, a lysosomal or endosomal protease. The linker can also be cleaved by a cleaving agent that is present in the extracellular environment (e.g., in the vicinity to the cellular membrane or tissue space). The linker can be, e.g., a peptidyl linker that is cleaved by an extracellular peptidase or protease enzyme, including, but not limited to, a cathepsin family enzyme or matrix metalloproteinases). In other embodiments, the cleavable linker is pH-sensitive, i.e., sensitive to hydrolysis at certain pH values. Typically, the pH-sensitive linker hydrolyzable under acidic conditions. For example, an acid- labile linker that is hydrolyzable in the lysosome (e.g., an oxime, hydrazone, semicarbazone, thiosemicarbazone, cis-aconitic amide, orthoester, acetal, ketal, or the like) can be used. (See, e.g., U.S. Pat. Nos.5,122,368; 5,824,805; 5,622,929; DUBOWCHIK AND WALKER, 1999, Pharm. Therapeutics 83:67-123; NEVILLE et. al., 1989, Biol. Chem.264:14653-14661.) In yet other embodiments, the linker is cleavable under reducing conditions known in the art. (See, e.g., Thorpe et al., 1987, Cancer Res.47:5924-5931; WAWRZYNCZAK et. al., In Immunoconjugates: Antibody Conjugates in Radioimagery and Therapy of Cancer (C. W. VOGEL ed., Oxford U. Press, 1987. See also U.S. Pat. No.4,880,935.). The linker can also be cleaved under reducing conditions found intra-cellularly (or extra-cellularly). For example, in a preferred embodiment, the specific linker N—O bond may be formally reduced and broken to result in a cleavage of the linker. In yet other specific embodiment, the linker is a malonate linker (Johnson et al., 1995, Anticancer Res.15:1387-93), a maleimidobenzoyl linker (Lau et al., 1995, Bioorg-Med- Chem.3(10):1299-1304), or a 3′-N-amide analog (Lau et al., 1995, Bioorg-Med-Chem.3(10):1305-12). In yet other embodiments, the linker unit is not cleavable, and the drug is released by antibody degradation. (See PCT Publication No. WO2012/166560 (Ambrx, Inc.) incorporated by reference herein in its entirety and for all purposes). Typically, the linker is not substantially sensitive to the extracellular environment. As used herein, “not substantially sensitive to the extracellular environment,” in the context of a linker, means that no more than about 20%, typically no more than about 15%, more typically no more than about 10%, and even more typically no more than about 5%, no more than about 3%, or no more than about 1% of the linkers, in a sample of antibody-drug conjugate compound, are cleaved when the antibody- drug conjugate compound presents in an extracellular environment (e.g., in plasma). Whether a linker is not substantially sensitive to the extracellular environment can be determined, for example, by incubating with plasma the antibody-drug conjugate compound for a predetermined time period (e.g., 2, 4, 8, 16, or 24 hours) and then quantitating the amount of free drug present in the plasma. In other, non-mutually exclusive embodiments, the linker promotes cellular internalization as known in the art. A variety of exemplary linkers that can be used with the present compositions and methods are described in WO 2004/010957, U.S. Publication No.2006/0074008, U.S. Publication No.20050238649, and U.S. Publication No.2006/0024317 (each of which is incorporated by reference herein in its entirety and for all purposes). For the purposes of the disclosure, a “Linker unit” (LU) is a bifunctional compound that can be used to link a Drug unit and an Antibody unit to form an antibody-drug conjugate compound. In some embodiments, the Linker unit has the formula: -A_a-W_w—Y_y— o wherein: -A- is a Stretcher unit, o a is 0 or 1, o each —W— is independently an Amino Acid unit, o w is an integer ranging from 0 to 12, o —Y— is a self-immolative Spacer unit, and o y is 0, 1 or 2. In some embodiments, a is 0 or 1, w is 0 or 1, and y is 0, 1 or 2. In some embodiments, a is 0 or 1, w is 0 or 1, and y is 0 or 1. In some embodiments, when w is 1 to 12, y is 1 or 2. In some embodiments, w is 2 to 12 and y is 1 or 2. In some embodiments, a is 1 and w and y are 0. V.) The Stretcher Unit The Stretcher unit (A), when present, is capable of linking an Antibody unit to an Amino Acid unit (—W—), if present, to a Spacer unit (—Y—), if present; or to a Drug unit (-D). Useful functional groups that can be present on a NECTIN-4 antibody, either naturally or via chemical manipulation include, but are not limited to, keto, aldehyde, sulfhydryl, amino, hydroxyl, the anomeric hydroxyl group of a carbohydrate, and carboxyl. Suitable functional groups are keto, aldehyde, sulfhydryl, and amino. In one example, the keto group is on a non-natural amino acid (nnAA) incorporated into the antibody of the invention. In a further example, the aldehyde group is on a nnAA incorporated into the antibody of the invention. In another example, sulfhydryl groups can be generated by reduction of the intramolecular disulfide bonds of a NECTIN-4 antibody. In another embodiment, sulfhydryl groups can be generated by reaction of an amino group of a lysine moiety of a NECTIN-4 antibody with 2- iminothiolane (Traut's reagent) or other sulfhydryl generating reagents. In certain embodiments, the NECTIN-4 antibody is a recombinant antibody and is engineered to carry one or more lysines. In certain other embodiments, the recombinant NECTIN-4antibody is engineered to carry additional sulfhydryl groups, e.g., additional cysteines. In one embodiment, the Stretcher unit forms a bond with a sulfur atom of the Antibody unit. The sulfur atom can be derived from a sulfhydryl group of an antibody. In certain embodiments, the Stretcher unit is linked to the Antibody unit via a disulfide bond between a sulfur atom of the Antibody unit and a sulfur atom of the Stretcher unit. In yet other embodiments, the Stretcher contains a reactive site that can form a bond with a primary or secondary amino group of an antibody. Examples of these reactive sites include, but are not limited to, activated esters such as succinimide esters, 4 nitrophenyl esters, pentafluorophenyl esters, tetrafluorophenyl esters, anhydrides, acid chlorides, sulfonyl chlorides, isocyanates and isothiocyanates. In some embodiments, the Stretcher contains a reactive site that is reactive to a modified carbohydrate's (—CHO) group that can be present on an antibody. For example, a carbohydrate can be mildly oxidized using a reagent such as sodium periodate and the resulting (—CHO) unit of the oxidized carbohydrate can be condensed with a Stretcher that contains a functionality such as a hydrazide, an oxime, a primary or secondary amine, a hydrazine, a thiosemicarbazone, a hydrazine carboxylate, and an arylhydrazide such as those described by Kaneko et al., 1991, Bioconjugate Chem.2:133-41. VI.) The Amino Acid Unit The Amino Acid unit (—W—), when present, links the Stretcher unit to the Spacer unit if the Spacer unit is present, links the Stretcher unit to the Drug moiety if the Spacer unit is absent, and links the Antibody unit to the Drug unit if the Stretcher unit and Spacer unit are absent. In certain embodiments, the Amino Acid unit can comprise natural amino acids. In other embodiments, the Amino Acid unit can comprise non-natural amino acids. In some embodiments, the Amino Acid unit can be enzymatically cleaved by one or more enzymes, including a cancer or tumor-associated protease, to liberate the Drug unit (-D), which in one embodiment is protonated in vivo upon release to provide a Drug (D). In one aspect of the Amino Acid unit, the Amino Acid unit is valine-citrulline (vc or Val-Cit). In another aspect, the Amino Acid unit is phenylalanine-lysine. In yet another aspect of the Amino Acid unit, the Amino Acid unit is N-methylvaline-citrulline. In yet another aspect, the Amino Acid unit is 5- aminovaleric acid, homo phenylalanine lysine, tetraisoquinolinecarboxylate lysine, cyclohexylalanine lysine, isonepecotic acid lysine, beta-alanine lysine, glycine serine valine glutamine and isonepecotic acid. VII.) The Spacer Unit The Spacer unit (—Y—), when present, links an Amino Acid unit to the Drug unit when an Amino Acid unit is present. Alternately, the Spacer unit links the Stretcher unit to the Drug unit when the Amino Acid unit is absent. The Spacer unit also links the Drug unit to the Antibody unit when both the Amino Acid unit and Stretcher unit are absent. Spacer units are of two general types: non self- immolative or self-immolative. Examples of possible spacers of the invention are known in the art. See, TOKI et. al., 2002, J. Org. Chem.67:1866-1872 and Nature Biotechnology 21(7):778-784). Other examples of self-immolative spacers include, but are not limited to, aromatic compounds that are electronically similar to the PAB group such as 2-aminoimidazol-5-methanol derivatives (HAY et. al., 1999, Bioorg. Med. Chem. Lett.9:2237) and ortho or para-aminobenzylacetals. Spacers can be used that undergo cyclization upon amide bond hydrolysis, such as substituted and unsubstituted 4-aminobutyric acid amides (RODRIGUES et. al., 1995, Chemistry Biology 2:223), appropriately substituted bicyclo[2.2.1] and bicyclo[2.2.2] ring systems (STORM et. al., 1972, J. Amer. Chem. Soc.94:5815) and 2-aminophenylpropionic acid amides (AMSBERRY et. al., 1990, J. Org. Chem.55:5867). Elimination of amine-containing drugs that are substituted at the a-position of glycine (KINGSBURY et. al., 1984, J. Med. Chem.27:1447) are also examples of self-immolative spacers. VIII.) The Drug Unit The Drug moiety (D) can be any cytotoxic, cytostatic, or immunomodulatory (e.g., immunosuppressive) drug. D is a Drug unit (moiety) having an atom that can form a bond with the Spacer unit, with the Amino Acid unit, with the Stretcher unit or with the Antibody unit. In some embodiments, the Drug unit D has a nitrogen atom that can form a bond with the Spacer unit. As used herein, the terms “Drug unit” and “Drug moiety” are synonymous and used interchangeably. Useful classes of cytotoxic, cytostatic, or immunomodulatory agents include, for example, antitubulin agents, DNA minor groove binders, DNA replication inhibitors, and alkylating agents. In some embodiments, the Drug 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. In some embodiments, the Drug Unit is a calicheamicin, camptothecin, a maytansinoid, or an anthracycline. In some embodiments the drug is a taxane, a topoisomerase inhibitor, a vinca alkaloid. In some typical embodiments, suitable cytotoxic agents include, for example, DNA minor groove binders (e.g., enediynes and lexitropsins, a CBI compound; see also U.S. Pat. No.6,130,237), duocarmycins, taxanes (e.g., paclitaxel and docetaxel), puromycins, and vinca alkaloids. Other cytotoxic agents include, for example, CC-1065, SN-38, topotecan, morpholino-doxorubicin, rhizoxin, cyanomorpholino-doxorubicin, echinomycin, combretastatin, netropsin, epothilone A and B, estramustine, cryptophysins, cemadotin, maytansinoids, discodermolide, eleutherobin, and mitoxantrone. In some embodiments, the Drug is an anti-tubulin agent. Examples of anti-tubulin agents include, auristatins, taxanes (e.g., Taxol® (paclitaxel), Taxotere® (docetaxel)), T67 (Tularik) and vinca alkyloids (e.g., vincristine, vinblastine, vindesine, and vinorelbine). Other antitubulin agents include, for example, baccatin derivatives, taxane analogs (e.g., epothilone A and B), nocodazole, colchicine and colcimid, estramustine, cryptophycins, cemadotin, maytansinoids, combretastatins, discodermolide, and eleutherobin. In certain embodiments, the cytotoxic agent is a maytansinoid, another group of anti-tubulin agents. For example, in specific embodiments, the maytansinoid is maytansine or DM-1 (ImmunoGen, Inc.; see also Chari et al., 1992, Cancer Res.52:127-131). In certain embodiments, the cytotoxic or cytostatic agent is a dolastatin. In certain embodiments, the cytotoxic or cytostatic agent is of the auristatin class, for example, Dolastatin-10, Auristatin e, or Auristatin PHE, etc. In certain embodiments, the Drug Unit (D) is an auristatin analog having the following structural formula:

or a pharmaceutically acceptable salt thereof, wherein R² R¹ is^O , wherein R² is a unsubstituted or substituted C₁-C₆ alkyl, heteroalkyl, cycloalkyl or cycloheteroalkyl; each of R^a, R^b and R^c is selected from H and NR^xR^y, provided that only one of R^a, R^b and R^c is NR^xR^y and each of the others is H; each of R^x and R^y is independently selected from R, R^r and L-R^z, provided that when one of R^x and R^y is L-R^z or R^r, the other is R; R⁵ is H or CR’₃, wherein each R’ is independently H or F; R⁶ is H or CH₂CN; L is a linker; R^r is (C=O)-O-(CH₂)_p-R^v or (C=O)-(CH₂)_q-R^v; R^v is R, OR, NHR, NR₂, an aryl group or an amino acid; p is 0, 1, 2, 3, 4, 5 or 6; q is 0, 1, 2, 3, 4, 5 or 6; R^z comprises a functional or reactive group; and R is H or a C₁-C₃ alkyl. IX.) Drug Loading Drug loading is represented by p and is the average number of Drug moieties per antibody in a molecule. Drug loading may range from 1 to 24 drug moieties (D) per antibody. ADCs of the invention include collections of antibodies conjugated with a range of drug moieties, from 1 to 24. The average number of drug moieties per antibody in preparations of ADC from conjugation reactions may be characterized by conventional means such as mass spectroscopy and, ELISA assay. The quantitative distribution of ADC in terms of p may also be determined. In some instances, separation, purification, and characterization of homogeneous ADC where p is a certain value from ADC with other drug loadings may be achieved by means such as electrophoresis. For some antibody-drug conjugates, p may be limited by the number of attachment sites on the antibody. For example, where the attachment is a cysteine thiol, as in the exemplary embodiments above, an antibody may have only one or several cysteine thiol groups, or may have only one or several sufficiently reactive thiol groups through which a linker may be attached. In certain embodiments, higher drug loading, e.g., p>5, may cause aggregation, insolubility, toxicity, or loss of cellular permeability of certain antibody-drug conjugates. In certain embodiments, the drug loading for an ADC of the invention ranges from 1 to about 8; from about 2 to about 6; from about 3 to about 5; from about 3 to about 4; from about 3.1 to about 3.9; from about 3.2 to about 3.8; from about 3.2 to about 3.7; from about 3.2 to about 3.6; from about 3.3 to about 3.8; or from about 3.3 to about 3.7. Indeed, it has been shown that for certain ADCs, the optimal ratio of drug moieties per antibody may be less than 8 and may be about 2 to about 5. See U.S. Pat. No.7,498,298 (herein incorporated by reference in its entirety). In certain embodiments, fewer than the theoretical maximum of drug moieties are conjugated to an antibody during a conjugation reaction. An antibody may contain, for example, lysine residues that do not react with the drug-linker intermediate or linker reagent, as discussed below. Generally, antibodies do not contain many free and reactive cysteine thiol groups which may be linked to a drug moiety; indeed most cysteine thiol residues in antibodies exist as disulfide bridges. In certain embodiments, an antibody may be reduced with a reducing agent such as dithiothreitol (DTT) or tricarbonylethylphosphine (TCEP), under partial or total reducing conditions, to generate reactive cysteine thiol groups. In certain embodiments, an antibody is subjected to denaturing conditions to reveal reactive nucleophilic groups such as lysine or cysteine. The loading (drug to antibody ratio) of an ADC may be controlled in different ways, e.g., by: (i) limiting the molar excess of drug-linker intermediate or linker reagent relative to antibody, (ii) limiting the conjugation reaction time or temperature, (iii) partial or limiting reductive conditions for cysteine thiol modification, (iv) engineering by recombinant techniques the amino acid sequence of the antibody such that the number and position of cysteine residues is modified for control of the number and/or position of linker-drug attachments (such as thioMab or thioFab prepared as disclosed herein and in WO2006/034488 (herein incorporated by reference in its entirety)). It is to be understood that where more than one nucleophilic group reacts with a drug-linker intermediate or linker reagent followed by drug moiety reagent, then the resulting product is a mixture of ADC compounds with a distribution of one or more drug moieties attached to an antibody. The average number of drugs per antibody may be calculated from the mixture by a dual ELISA antibody assay, which is specific for antibody and specific for the drug. Individual ADC molecules may be identified in the mixture by mass spectroscopy and separated by HPLC, e.g. hydrophobic interaction chromatography (see, e.g., Hamblett, K. J., et al. “Effect of drug loading on the pharmacology, pharmacokinetics, and toxicity of an anti-CD30 antibody-drug conjugate,” Abstract No.624, American Association for Cancer Research, 2004 Annual Meeting, Mar.27-31, 2004, Proceedings of the AACR, Volume 45, March 2004; Alley, S. C., et al. “Controlling the location of drug attachment in antibody-drug conjugates,” Abstract No.627, American Association for Cancer Research, 2004 Annual Meeting, Mar.27-31, 2004, Proceedings of the AACR, Volume 45, March 2004). In certain embodiments, a homogeneous ADC with a single loading value may be isolated from the conjugation mixture by electrophoresis or chromatography. X.) Methods of Determining Cytotoxic Effect of ADCs Methods of determining whether a Drug or Antibody-Drug conjugate exerts a cytostatic and/or cytotoxic effect on a cell are known. Generally, the cytotoxic or cytostatic activity of an ADC can be measured by: exposing mammalian cells expressing a target protein of the Antibody Drug conjugate in a cell culture medium; culturing the cells for a period from about 6 hours to about 5 days; and measuring cell viability. Cell-based in vitro assays can be used to measure viability (proliferation), cytotoxicity, and induction of apoptosis (caspase activation) of the Antibody Drug conjugate. For determining whether an ADC exerts a cytostatic effect, a thymidine incorporation assay may be used. For example, cancer cells expressing a target antigen at a density of 5,000 cells/well of a 96-well plated can be cultured for a 72-hour period and exposed to 0.5 μCi of³H-thymidine during the final 8 hours of the 72-hour period. The incorporation of³H-thymidine into cells of the culture is measured in the presence and absence of the ADC. For determining cytotoxicity, necrosis, or apoptosis (programmed cell death) can be measured. Necrosis is typically accompanied by increased permeability of the plasma membrane; swelling of the cell, and rupture of the plasma membrane. Apoptosis is typically characterized by membrane blebbing, condensation of cytoplasm, and the activation of endogenous endonucleases. Determination of any of these effects on cancer cells indicates that an ADC is useful in the treatment of cancers. Cell viability can be measured by determining in a cell the uptake of a dye such as neutral red, trypan blue, or ALAMAR™ blue (see, e.g., PAGE et. al., 1993, Intl. J. Oncology 3:473-476). In such an assay, the cells are incubated in media containing the dye, the cells are washed, and the remaining dye, reflecting cellular uptake of the dye, is measured spectrophotometrically. The protein-binding dye sulforhodamine B (SRB) can also be used to measure cytotoxicity (SKEHAN et. al., 1990, J. Natl. Cancer Inst.82:1107-12). Alternatively, a tetrazolium salt, such as MTT, or CellTiter-Glo ^, is used in a quantitative assay for mammalian cell survival and proliferation by detecting living, but not dead, cells (see, e.g., MOSMANN, 1983, J. Immunol. Methods 65:55-63). Apoptosis can be quantitated by measuring, for example, DNA fragmentation. Commercial photometric methods for the quantitative in vitro determination of DNA fragmentation are available. Examples of such assays, including TUNEL (which detects incorporation of labeled nucleotides in fragmented DNA) and ELISA-based assays, are described in Biochemica, 1999, no.2, pp.34-37 (Roche Molecular Biochemicals). Apoptosis can also be determined by measuring morphological changes in a cell. For example, as with necrosis, loss of plasma membrane integrity can be determined by measuring the uptake of certain dyes (e.g., a fluorescent dye such as, for example, acridine orange or ethidium bromide). A method for measuring apoptotic cell number has been described by Duke and Cohen, Current Protocols in Immunology (COLIGAN et. al. eds., 1992, pp.3.17.1-3.17.16). Cells also can be labeled with a DNA dye (e.g., acridine orange, ethidium bromide, or propidium iodide) and the cells observed for chromatin condensation and margination along the inner nuclear membrane. Other morphological changes that can be measured to determine apoptosis include, e.g., cytoplasmic condensation, increased membrane blebbing, and cellular shrinkage. The presence of apoptotic cells can be measured in both the attached and “floating” compartments of the cultures. For example, both compartments can be collected by removing the supernatant, trypsinizing the attached cells, combining the preparations following a centrifugation wash step (e.g., 10 minutes at 2000 rpm), and detecting apoptosis (e.g., by measuring DNA fragmentation). (See, e.g., PIAZZA et. al., 1995, Cancer Research 55:3110-16). In vivo, the effect of a NECTIN-4 antibody therapeutic composition can be evaluated in a suitable animal model. For example, xenogeneic cancer models can be used, wherein cancer explants or passaged xenograft tissues are introduced into immune compromised animals, such as nude or SCID mice (KLEIN et. al., 1997, Nature Medicine 3: 402-408). For example, PCT Patent Application WO98/16628 and U.S. Pat. No.6,107,540 describe various xenograft models of human prostate cancer capable of recapitulating the development of primary tumors, micro-metastasis, and the formation of osteoblastic metastases characteristic of late-stage disease. Efficacy can be predicted using assays that measure inhibition of tumor formation, tumor regression or metastasis, and the like. In vivo assays that evaluate the promotion of apoptosis are useful in evaluating therapeutic compositions. In one embodiment, xenografts from tumor bearing mice treated with therapeutic composition can be examined for the presence of apoptotic foci and compared to untreated control xenograft-bearing mice. The extent to which apoptotic foci are found in the tumors of the treated mice provides an indication of the therapeutic efficacy of the composition. The therapeutic compositions used in the practice of the foregoing methods can be formulated into pharmaceutical compositions comprising a carrier suitable for the desired delivery method. Suitable carriers include any material that when combined with the therapeutic composition retains the anti-tumor function of the therapeutic composition and is generally non-reactive with the patient's immune system. Examples include, but are not limited to, any of a number of standard pharmaceutical carriers such as sterile phosphate buffered saline solutions, bacteriostatic water, and the like (See, generally, Remington's Pharmaceutical Sciences 16th Edition, A. Osal., Ed., 1980). Therapeutic formulations can be solubilized and administered via any route capable of delivering the therapeutic composition to the tumor site. Potentially effective routes of administration include, but are not limited to, intravenous, parenteral, intraperitoneal, intramuscular, intratumor, intradermal, intra-organ, orthotopic, and the like. A preferred formulation for intravenous injection comprises the therapeutic composition in a solution of preserved bacteriostatic water, sterile unpreserved water, and/or diluted in polyvinylchloride or polyethylene bags containing 0.9% sterile Sodium Chloride for Injection, USP. Therapeutic protein preparations can be lyophilized and stored as sterile powders, preferably under vacuum, and then reconstituted in bacteriostatic water (containing for example, benzyl alcohol preservative) or in sterile water prior to injection. Dosages and administration protocols for the treatment of cancers using the foregoing methods will vary with the method and the target cancer, and will generally depend on a number of other factors appreciated in the art. In one embodiment, the pharmaceutical composition of the present invention may comprise more than one species of ADC of the invention due to modification of a NECTIN-4 antibody. For example, the present invention includes a pharmaceutical composition comprising the ADC of the invention, wherein the NECTIN-4 antibody is an antibody with a C-terminal lysine partially removed or completely removed an antibody having N-terminal post-translational modification, an antibody lacking heavy chain C-terminal lysine and having N-terminal post-translational modification, and/or an antibody having heavy chain C-terminal lysine and not having N-terminal post-translational modification. In a preferred embodiment, NECTIN-4 antibody is set forth in Table(s) VI and Table VII. XI.) Treatment of Cancer(s) Expressing NECTIN-4 The identification of NECTIN-4 as a protein that is normally expressed in a restricted set of tissues or cells, but which is also expressed in cancers such as those listed in Table I, opens a number of therapeutic approaches to the treatment of such cancers. Of note, targeted antitumor therapies have been useful even when the targeted protein is expressed on normal tissues or cells, even vital normal organ tissues. A vital organ is one that is necessary to sustain life, such as the heart or colon. A non-vital organ is one that can be removed whereupon the individual is still able to survive. Examples of non-vital organs are ovary, breast, and prostate. Expression of a target protein in normal tissue, even vital normal tissue, does not defeat the utility of a targeting agent for the protein as a therapeutic for certain tumors in which the protein is also overexpressed. For example, expression in vital organs is not in and of itself detrimental. In addition, organs regarded as dispensable, such as the prostate and ovary, can be removed without affecting mortality. Finally, some vital organs are not affected by normal organ expression because of an immunoprivilege. Immunoprivileged organs are organs that are protected from blood by a blood-organ barrier and thus are not accessible to immunotherapy. Examples of immunoprivileged organs are the brain and testis. Accordingly, therapeutic approaches that inhibit the activity of a NECTIN-4 protein are useful for patients suffering from cancer that expresses NECTIN-4 (such as, for example, those cancers set forth in Table I). These therapeutic approaches generally fall into three classes. The first class modulates NECTIN-4 function as it relates to tumor cell growth leading to inhibition or retardation of tumor cell growth or inducing its killing. The second class comprises various methods for inhibiting the binding or association of a NECTIN-4 protein with its binding partner or with other proteins. The third class comprises a variety of methods for inhibiting the transcription of a NECTIN-4 gene or translation of NECTIN-4 mRNA. Accordingly, cancer patients can be evaluated for the presence and level of NECTIN-4 expression, preferably using immunohistochemical assessments of tumor tissue, quantitative NECTIN-4 imaging, or other techniques that reliably indicate the presence and degree of NECTIN-4 expression. Immunohistochemical analysis of tumor biopsies or surgical specimens is preferred for this purpose, if applicable. Methods for immunohistochemical analysis of tumor tissues are well known in the art. XII.) NECTIN-4 ADC Cocktails Therapeutic methods of the invention contemplate the administration of single NECTIN-4 ADCs as well as combinations, or cocktails, of different antibodies (i.e., NECTIN-4 antibodies or antibodies that bind another protein). Such antibody cocktails can have certain advantages in as much as they contain antibodies that target different epitopes, exploit different effector mechanisms, or combine directly cytotoxic antibodies with antibodies that rely on immune effector functionality. Such antibodies in combination can exhibit synergistic therapeutic effects. In addition, NECTIN-4 antibodies can be administered concomitantly with other therapeutic modalities, including but not limited to various chemotherapeutic and biologic agents, androgen-blockers, immune modulators (e.g., IL-2, GM-CSF, PD1, PD-L1), surgery or radiation. In a preferred embodiment, the NECTIN-4 antibodies are administered in conjugated form. In a further preferred embodiment, the NECTIN-4 antibodies are set forth in Table VI and Table VII. NECTIN-4 ADC formulations are administered via any route capable of delivering the antibodies to a tumor cell. Routes of administration include, but are not limited to, intravenous, intraperitoneal, intramuscular, intratumor, intradermal, and the like. Treatment generally involves repeated administration of the NECTIN-4 ADC preparation, via an acceptable route of administration such as intravenous injection (IV), typically at a dose in the range, including but not limited to, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25 mg/kg body weight. In general, doses in the range of 10-1000 mg MAb per week are effective and well tolerated. Based on clinical experience with the Herceptin® (Trastuzumab) in the treatment of metastatic breast cancer, an initial loading dose of approximately 4 mg/kg patient body weight IV, followed by weekly doses of about 2 mg/kg IV of the MAb preparation represents an acceptable dosing regimen. Preferably, the initial loading dose is administered as a 90-minute or longer infusion. The periodic maintenance dose is administered as a 30 minute or longer infusion, provided the initial dose was well tolerated. As appreciated by those of skill in the art, numerous factors can influence the ideal dose regimen in a particular case. Such factors include, for example, the binding affinity and half-life of the antibodies used, the degree of NECTIN-4 expression in the patient, the extent of circulating shed NECTIN-4 antigen, the desired steady-state antibody concentration level, frequency of treatment, and the influence of chemotherapeutic or other agents used in combination with the treatment method of the invention, as well as the health status of a particular patient. Optionally, patients should be evaluated for the levels of NECTIN-4 in a given sample (e.g., the levels of circulating NECTIN-4 antigen and/or NECTIN-4 expressing cells) in order to assist in the determination of the most effective dosing regimen, etc. Such evaluations are also used for monitoring purposes throughout therapy and are useful to gauge therapeutic success in combination with the evaluation of other parameters (for example, urine cytology and/or ImmunoCyt levels in bladder cancer therapy, or by analogy, serum PSA levels in prostate cancer therapy). An object of the present invention is to provide NECTIN-4 ADCs, which inhibit or retard the growth of tumor cells expressing NECTIN-4. A further object of this invention is to provide methods to inhibit angiogenesis and other biological functions and thereby reduce tumor growth in mammals, preferably humans, using such NECTIN-4 ADCs, and in particular using such NECTIN-4 ADCs combined with other drugs or immunologically active treatments. XIII.) Combination Therapy In one embodiment, there is synergy when tumors, including human tumors, are treated with NECTIN-4 ADCs in conjunction with chemotherapeutic agents or radiation or combinations thereof. In other words, the inhibition of tumor growth by a NECTIN-4 ADC is enhanced more than expected when combined with chemotherapeutic agents or radiation or combinations thereof. Synergy may be shown, for example, by greater inhibition of tumor growth with combined treatment than would be expected from a treatment of only NECTIN-4 ADC or the additive effect of treatment with a NECTIN-4 ADC and a chemotherapeutic agent or radiation. Preferably, synergy is demonstrated by remission of the cancer where remission is not expected from treatment either from a NECTIN-4 ADC or with treatment using an additive combination of a NECTIN-4 ADC and a chemotherapeutic agent or radiation or an immunotherapy such as CAR-T or NK cell therapy. The method for inhibiting growth of tumor cells using a NECTIN-4 ADC and a combination of chemotherapy or radiation or both comprises administering the NECTIN-4 ADC before, during, or after commencing chemotherapy or radiation therapy, as well as any combination thereof (i.e. before and during, before and after, during and after, or before, during, and after commencing the chemotherapy and/or radiation therapy). For example, the NECTIN-4 ADC is typically administered between 1 and 60 days, preferably between 3 and 40 days, more preferably between 5 and 12 days before commencing radiation therapy and/or chemotherapy. However, depending on the treatment protocol and the specific patient’s needs, the method is performed in a manner that will provide the most efficacious treatment and ultimately prolong the life of the patient. The administration of chemotherapeutic agents can be accomplished in a variety of ways including systemically by the parenteral and enteral routes. In one embodiment, the NECTIN-4 ADCs and the chemotherapeutic agent are administered as separate molecules. Particular examples of chemotherapeutic agents or chemotherapy include cisplatin, dacarbazine (DTIC), dactinomycin, mechlorethamine (nitrogen mustard), streptozocin, cyclophosphamide, carmustine (BCNU), lomustine (CCNU), doxorubicin (adriamycin), daunorubicin, procarbazine, mitomycin, cytarabine, etoposide, methotrexate, 5-fluorouracil, vinblastine, vincristine, bleomycin, paclitaxel (taxol), docetaxel (taxotere), aldesleukin, asparaginase, busulfan, carboplatin, cladribine, dacarbazine, floxuridine, fludarabine, hydroxyurea, ifosfamide, interferon alpha, leuprolide, megestrol, melphalan, mercaptopurine, plicamycin, mitotane, pegaspargase, pentostatin, pipobroman, plicamycin, streptozocin, tamoxifen, teniposide, testolactone, thioguanine, thiotepa, uracil mustard, vinorelbine, gemcitabine, chlorambucil, taxol and combinations thereof. The source of radiation, used in combination with a NECTIN-4 ADC, can be either external or internal to the patient being treated. When the source is external to the patient, the therapy is known as external beam radiation therapy (EBRT). When the source of radiation is internal to the patient, the treatment is called brachytherapy (BT). In one embodiment, the radiation therapy is boron neutron capture therapy. In one embodiment, the radiation is Proton Boron Fusion Therapy. The above-described therapeutic regimens may be further combined with additional cancer treating agents and/or regimes, for example additional chemotherapy, cancer vaccines, signal transduction inhibitors, agents useful in treating abnormal cell growth or cancer, antibodies (e.g. Anti- CTLA-4 antibodies as described in WO/2005/092380 (Pfizer)) or other ligands that inhibit tumor growth by binding to IGF-1R, and cytokines. When the mammal is subjected to additional chemotherapy, chemotherapeutic agents described above may be used. Additionally, growth factor inhibitors, biological response modifiers, anti- hormonal therapy, selective estrogen receptor modulators (SERMs), angiogenesis inhibitors, and anti- androgens may be used. For example, anti-hormones, for example anti-estrogens such as Nolvadex (tamoxifen) or, anti-androgens such as Casodex (4′-cyano-3-(4-fluorophenylsulphonyl)-2-hydroxy-2- methyl-3-′-(trifluoromethyl)propionanilide) may be used. The above therapeutic approaches can be combined with any one of a wide variety of surgical, chemotherapy or radiation therapy regimens. The therapeutic approaches of the invention can enable the use of reduced dosages of chemotherapy (or other therapies) and/or less frequent administration, an advantage for all patients and particularly for those that do not tolerate the toxicity of the chemotherapeutic agent well. XIV.) Kits/Articles of Manufacture For use in the laboratory, prognostic, prophylactic, diagnostic and therapeutic applications described herein, kits are within the scope of the invention. Such kits can comprise a carrier, package, or container that is compartmentalized to receive one or more containers such as vials, tubes, and the like, each of the container(s) comprising one of the separate elements to be used in the method, along with a label or insert comprising instructions for use, such as a use described herein. For example, the container(s) can comprise a NECTIN-4 antibody or several NECTIN-4 antibodies (See, Tables VI and VII) of the disclosure. Kits can comprise a container comprising a drug unit. The kit can include all or part of the NECTIN-4 ADCs and/or diagnostic assays for detecting cancer and/or other immunological disorders. The kit of the invention will typically comprise the container described above, and one or more other containers associated therewith that comprise materials desirable from a commercial and user standpoint, including buffers, diluents, filters, needles, syringes; carrier, package, container, vial and/or tube labels listing contents and/or instructions for use, and package inserts with instructions for use. A label can be present on or with the container to indicate that the composition is used for a specific therapy or non-therapeutic application, such as a prognostic, prophylactic, diagnostic or laboratory application, and can also indicate directions for either in vivo or in vitro use, such as those described herein. Directions and or other information can also be included on an insert(s) or label(s) which is included with or on the kit. The label can be on or associated with the container. A label can be on a container when letters, numbers or other characters forming the label are molded or etched into the container itself; a label can be associated with a container when it is present within a receptacle or carrier that also holds the container, e.g., as a package insert. The label can indicate that the composition is used for diagnosing, treating, prophylaxing or prognosing a condition, such as a cancer or other immunological disorder. The terms “kit” and “article of manufacture” can be used as synonyms. In another embodiment of the invention, an article(s) of manufacture containing compositions, such as NECTIN-4 ADCs of the disclosure. The article of manufacture typically comprises at least one container and at least one label. Suitable containers include, for example, bottles, vials, syringes, and test tubes. The containers can be formed from a variety of materials such as glass, metal, or plastic. The container can hold one or several NECTIN-4 ADCs and/or one or more therapeutics doses of NECTIN-4 ADCs. The container can alternatively hold a composition that is effective for treating, diagnosis, prognosing or prophylaxing a condition and can have a sterile access port (for example the container can be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). The active agents in the composition can be a NECTIN-4 antibody or ADC of the present disclosure. The article of manufacture can further comprise a second container comprising a pharmaceutically acceptable buffer, such as phosphate-buffered saline, Ringer's solution and/or dextrose solution. It can further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, stirrers, needles, syringes, and/or package inserts with indications and/or instructions for use. EXEMPLARY EMBODIMENTS 1) An antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 52, SEQ ID NO: 53, and SEQ ID NO: 54. 2) The antibody or antigen binding fragment thereof of claim 1, further comprising a light chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 70, SEQ ID NO: 71, and SEQ ID NO: 72. 3) The antibody or antigen binding fragment thereof of claim 1, wherein the heavy chain variable region comprises the sequence set forth in SEQ ID NO: 28. 4) The antibody or antigen binding fragment thereof of claim 2, wherein the light chain variable region comprises the sequence set forth in SEQ ID NO: 34. 5) The antibody or antigen binding fragment thereof of claim 1, wherein the heavy chain comprises the sequence set forth in SEQ ID NO: 5. 6) The antibody or antigen binding fragment thereof of claim 2, wherein the light chain comprises the sequence set forth in SEQ ID NO: 17. 7) The antibody or antigen binding fragment thereof of claim 1, comprising a heavy chain variable region comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homologous to the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 28 and a light chain variable region comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homologous to the light chain variable region amino acid sequence set forth in SEQ ID NO: 34. 8) The antibody or antigen binding fragment thereof of claim 1, wherein the antigen binding fragment thereof is a Fab, F(ab′)2, Fv or scFv. 9) The antibody or antigen binding fragment thereof of claim 1, wherein the antibody is a fully human antibody. ) The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof is recombinantly produced. ) The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof is conjugated to a drug via a linker. ) The antibody or antigen binding fragment thereof of claim 11, wherein the drug is an auristatin analog. ) The antibody or antigen binding fragment thereof of claim 11, further comprising a stretcher unit. ) The antibody or antigen binding fragment thereof of claim 11, further comprising a spacer unit. ) The antibody or antigen binding fragment thereof of claim 11, further comprising an amino acid unit. ) A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of any of claims 1-15 and a pharmaceutically acceptable excipient. ) A kit comprising the antibody or antigen binding fragment thereof of any of claims 1-16.) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 16. ) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the kit of claim 17. ) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of any of claims 1-15. ) The method of any of claim 18-20, wherein the subject is a human subject. ) The method of claim 21, wherein the cancer is set forth in Table I. ) The method of claim 22, wherein the method further comprises administering radiation or a chemotherapeutic agent. ) An antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57. ) The antibody or antigen binding fragment thereof of claim 24, further comprising a light chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 73, SEQ ID NO: 74, and SEQ ID NO: 75. ) The antibody or antigen binding fragment thereof of claim 24, wherein the heavy chain variable region comprises the sequence set forth in SEQ ID NO: 29. ) The antibody or antigen binding fragment thereof of claim 24, wherein the light chain variable region comprises the sequence set forth in SEQ ID NO: 35. ) The antibody or antigen binding fragment thereof of claim 24, wherein the heavy chain comprises the sequence set forth in SEQ ID NO: 6. ) The antibody or antigen binding fragment thereof of claim 24, wherein the light chain comprises the sequence set forth in SEQ ID NO: 18. ) The antibody or antigen binding fragment thereof of claim 24, comprising a heavy chain variable region comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homologous to the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 29 and a light chain variable region comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homologous to the light chain variable region amino acid sequence set forth in SEQ ID NO: 35. ) The antibody or antigen binding fragment thereof of claim 24, wherein the antigen binding fragment thereof is a Fab, F(ab′)2, Fv or scFv. ) The antibody or antigen binding fragment thereof of claim 24, wherein the antibody is a fully human antibody. ) The antibody or antigen binding fragment thereof of claim 24, wherein the antibody or antigen binding fragment thereof is recombinantly produced. ) The antibody or antigen binding fragment thereof of claim 24, wherein the antibody or antigen binding fragment thereof is conjugated to a drug via a linker. ) The antibody or antigen binding fragment thereof of claim 34, wherein the drug is an auristatin analog. ) The antibody or antigen binding fragment thereof of claim 34, further comprising a stretcher unit. ) The antibody or antigen binding fragment thereof of claim 34, further comprising a spacer unit. ) The antibody or antigen binding fragment thereof of claim 34, further comprising an amino acid unit. ) A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of any of claims 24-38 and a pharmaceutically acceptable excipient. ) A kit comprising the antibody or antigen binding fragment thereof of any of claims 24-39.) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 39. ) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the kit of claim 40. ) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of any of claims 24-39. ) The method of any of claim 41-43, wherein the subject is a human subject. ) The method of claim 43, wherein the cancer is set forth in Table I. ) The method of claim 43, wherein the method further comprises administering radiation or a chemotherapeutic agent. ) An antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 58, SEQ ID NO: 59, and SEQ ID NO: 60. ) The antibody or antigen binding fragment thereof of claim 47, further comprising a light chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 76, SEQ ID NO: 77, and SEQ ID NO: 78. ) The antibody or antigen binding fragment thereof of claim 47, wherein the heavy chain variable region comprises the sequence set forth in SEQ ID NO: 30. ) The antibody or antigen binding fragment thereof of claim 47, wherein the light chain variable region comprises the sequence set forth in SEQ ID NO: 36. ) The antibody or antigen binding fragment thereof of claim 47, wherein the heavy chain comprises the sequence set forth in SEQ ID NO: 8. ) The antibody or antigen binding fragment thereof of claim 47, wherein the light chain comprises the sequence set forth in SEQ ID NO: 20. ) The antibody or antigen binding fragment thereof of claim 47, comprising a heavy chain variable region comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homologous to the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 30 and a light chain variable region comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homologous to the light chain variable region amino acid sequence set forth in SEQ ID NO: 36. ) The antibody or antigen binding fragment thereof of claim 47, wherein the antigen binding fragment thereof is a Fab, F(ab′)2, Fv or scFv. ) The antibody or antigen binding fragment thereof of claim 47, wherein the antibody is a fully human antibody. ) The antibody or antigen binding fragment thereof of claim 47, wherein the antibody or antigen binding fragment thereof is recombinantly produced. ) The antibody or antigen binding fragment thereof of claim 47, wherein the antibody or antigen binding fragment thereof is conjugated to a drug via a linker. ) The antibody or antigen binding fragment thereof of claim 47, wherein the drug is an auristatin analog. ) The antibody or antigen binding fragment thereof of claim 47, further comprising a stretcher unit. ) The antibody or antigen binding fragment thereof of claim 47, further comprising a spacer unit. ) The antibody or antigen binding fragment thereof of claim 47, further comprising an amino acid unit. ) A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of any of claims 47-61 and a pharmaceutically acceptable excipient. ) A kit comprising the antibody or antigen binding fragment thereof of any of claims 47-62.) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 62. ) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the kit of claim 63. ) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of any of claims 47-65. ) The method of any of claim 64-66, wherein the subject is a human subject. ) The method of claim 66, wherein the cancer is set forth in Table I. ) The method of claim 66, wherein the method further comprises administering radiation or a chemotherapeutic agent. ) An antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 61, SEQ ID NO: 62, and SEQ ID NO: 63. ) The antibody or antigen binding fragment thereof of claim 70, further comprising a light chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 79, SEQ ID NO: 80, and SEQ ID NO: 81. ) The antibody or antigen binding fragment thereof of claim 70, wherein the heavy chain variable region comprises the sequence set forth in SEQ ID NO: 31. ) The antibody or antigen binding fragment thereof of claim 70, wherein the light chain variable region comprises the sequence set forth in SEQ ID NO: 37. ) The antibody or antigen binding fragment thereof of claim 70, wherein the heavy chain comprises the sequence set forth in SEQ ID NO: 10. ) The antibody or antigen binding fragment thereof of claim 70, wherein the light chain comprises the sequence set forth in SEQ ID NO: 22. ) The antibody or antigen binding fragment thereof of claim 70, comprising a heavy chain variable region comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homologous to the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 31 and a light chain variable region comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homologous to the light chain variable region amino acid sequence set forth in SEQ ID NO: 37. ) The antibody or antigen binding fragment thereof of claim 70, wherein the antigen binding fragment thereof is a Fab, F(ab′)2, Fv or scFv. ) The antibody or antigen binding fragment thereof of claim 70, wherein the antibody is a fully human antibody. ) The antibody or antigen binding fragment thereof of claim 70, wherein the antibody or antigen binding fragment thereof is recombinantly produced. ) The antibody or antigen binding fragment thereof of claim 70, wherein the antibody or antigen binding fragment thereof is conjugated to a drug via a linker. ) The antibody or antigen binding fragment thereof of claim 70, wherein the drug is an auristatin analog. ) The antibody or antigen binding fragment thereof of claim 70, further comprising a stretcher unit. ) The antibody or antigen binding fragment thereof of claim 70, further comprising a spacer unit. ) The antibody or antigen binding fragment thereof of claim 70, further comprising an amino acid unit. ) A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of any of claims 70-84 and a pharmaceutically acceptable excipient. ) A kit comprising the antibody or antigen binding fragment thereof of any of claims 70-84.) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 85. ) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the kit of claim 86. ) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of any of claims 70-88. ) The method of any of claim 87-89, wherein the subject is a human subject. ) The method of claim 89, wherein the cancer is set forth in Table I. ) The method of claim 89, wherein the method further comprises administering radiation or a chemotherapeutic agent. ) An antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 64, SEQ ID NO: 65, and SEQ ID NO: 66. ) The antibody or antigen binding fragment thereof of claim 93, further comprising a light chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 82, SEQ ID NO: 83, and SEQ ID NO: 84. ) The antibody or antigen binding fragment thereof of claim 93, wherein the heavy chain variable region comprises the sequence set forth in SEQ ID NO: 32. ) The antibody or antigen binding fragment thereof of claim 93, wherein the light chain variable region comprises the sequence set forth in SEQ ID NO: 38. ) The antibody or antigen binding fragment thereof of claim 93, wherein the heavy chain comprises the sequence set forth in SEQ ID NO: 12. ) The antibody or antigen binding fragment thereof of claim 93, wherein the light chain comprises the sequence set forth in SEQ ID NO: 24. ) The antibody or antigen binding fragment thereof of claim 93, comprising a heavy chain variable region comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homologous to the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 32 and a light chain variable region comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homologous to the light chain variable region amino acid sequence set forth in SEQ ID NO: 38. 0) The antibody or antigen binding fragment thereof of claim 93, wherein the antigen binding fragment thereof is a Fab, F(ab′)2, Fv or scFv. 1) The antibody or antigen binding fragment thereof of claim 93, wherein the antibody is a fully human antibody. 2) The antibody or antigen binding fragment thereof of claim 93, wherein the antibody or antigen binding fragment thereof is recombinantly produced. 3) The antibody or antigen binding fragment thereof of claim 93, wherein the antibody or antigen binding fragment thereof is conjugated to a drug via a linker. 4) The antibody or antigen binding fragment thereof of claim 93, wherein the drug is an auristatin analog. 5) The antibody or antigen binding fragment thereof of claim 93, further comprising a stretcher unit. 6) The antibody or antigen binding fragment thereof of claim 93, further comprising a spacer unit. 7) The antibody or antigen binding fragment thereof of claim 93, further comprising an amino acid unit. 8) A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of any of claims 93-107 and a pharmaceutically acceptable excipient. 9) A kit comprising the antibody or antigen binding fragment thereof of any of claims 93- 108. 0) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 108. 1) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the kit of claim 109. ) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of any of claims 93-107. ) The method of any of claim 110-112, wherein the subject is a human subject. ) The method of claim 112, wherein the cancer is set forth in Table I. ) The method of claim 112, wherein the method further comprises administering radiation or a chemotherapeutic agent. ) An antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 67, SEQ ID NO: 68, and SEQ ID NO: 69. ) The antibody or antigen binding fragment thereof of claim 116, further comprising a light chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 85, SEQ ID NO: 86, and SEQ ID NO: 87. ) The antibody or antigen binding fragment thereof of claim 116, wherein the heavy chain variable region comprises the sequence set forth in SEQ ID NO: 33. ) The antibody or antigen binding fragment thereof of claim 116, wherein the light chain variable region comprises the sequence set forth in SEQ ID NO: 39. ) The antibody or antigen binding fragment thereof of claim 116, wherein the heavy chain comprises the sequence set forth in SEQ ID NO: 14. ) The antibody or antigen binding fragment thereof of claim 116, wherein the light chain comprises the sequence set forth in SEQ ID NO: 26. ) The antibody or antigen binding fragment thereof of claim 116, comprising a heavy chain variable region comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homologous to the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 33 and a light chain variable region comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homologous to the light chain variable region amino acid sequence set forth in SEQ ID NO: 39. ) The antibody or antigen binding fragment thereof of claim 116, wherein the antigen binding fragment thereof is a Fab, F(ab′)2, Fv or scFv. ) The antibody or antigen binding fragment thereof of claim 116, wherein the antibody is a fully human antibody. ) The antibody or antigen binding fragment thereof of claim 116, wherein the antibody or antigen binding fragment thereof is recombinantly produced. ) The antibody or antigen binding fragment thereof of claim 116, wherein the antibody or antigen binding fragment thereof is conjugated to a drug via a linker. ) The antibody or antigen binding fragment thereof of claim 116, wherein the drug is an auristatin analog. 8) The antibody or antigen binding fragment thereof of claim 116, further comprising a stretcher unit. 9) The antibody or antigen binding fragment thereof of claim 116, further comprising a spacer unit. 0) The antibody or antigen binding fragment thereof of claim 116, further comprising an amino acid unit. 1) A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of any of claims 116-130 and a pharmaceutically acceptable excipient. 2) A kit comprising the antibody or antigen binding fragment thereof of any of claims 116- 131. 3) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 131. 4) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the kit of claim 132. 5) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of any of claims 116-130. 6) The method of any of claim 133-135, wherein the subject is a human subject. 7) The method of claim 135, wherein the cancer is set forth in Table I. 8) The method of claim 135, wherein the method further comprises administering radiation or a chemotherapeutic agent or CAR-T therapy, or NK cell therapy. 9) An antibody drug conjugate (ADC) comprising a NECTIN-4 antibody or antigen binding fragment thereof conjugated to a Drug-Linker (DL) payload, wherein the antibody or antigen binding fragment thereof comprises a heavy chain CDR region comprising an amino acid sequence set forth in any of SEQ ID NO: 52 through SEQ IS NO: 69. 0) The ADC of claim 139, further comprising a NECTIN-4 antibody or antigen binding fragment thereof wherein the antibody or antigen binding fragment thereof comprises a light chain CDR region comprising an amino acid sequence set forth in any of SEQ ID NO: 70 through SEQ ID NO: 87. 1) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure:

. 142) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure:

. 143) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure:

. 144) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure:

. 145) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure:

. 146) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure:

147) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure: N . 8) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure:

. 9) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure:

. 0) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure: N

. 1) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure:

. 2) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure:_N

. 3) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure:_N

. 4) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure:

. 5) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure: N

. 6) The ADC of claim 139 or 140, wherein the DL payload comprises the following chemical structure: N

. 7) A pharmaceutical composition comprising the ADCs of any of claims 139 through 156 and a pharmaceutically acceptable excipient. 8) A kit comprising the ADC of any of claims 139-156. 9) A kit comprising the pharmaceutical composition of claim 157. 0) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of an ADC of any of claims 139-156. 161) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 157. 162) The method of claim 160, wherein the subject is a human. 163) The method of claim 161, wherein the subject is a human. 164) The method of claim 160, wherein the cancer is set forth in Table I. 165) The method of claim 161, wherein the cancer is set forth in Table I. 166) The method of claim 160, wherein the method further comprises administering radiation or a chemotherapeutic agent or CAR-T therapy, or NK cell therapy. 167) The method of claim 161, wherein the method further comprises administering radiation or a chemotherapeutic agent or CAR-T therapy, or NK cell therapy. EXAMPLES: Various aspects of the invention are further described and illustrated by way of the several examples that follow, none of which is intended to limit the scope of the invention. Example 1: Methods of Generating Antibodies. The NECTIN-4 antibodies were generated by de novo discovery campaign using yeast display human Fab antibody libraries. After several rounds of enrichment followed by clone screening, clones that specifically recognize human Nectin-4 expressed on cancer cells were identified. Subsequently, the variable heavy and light chains of the antibody were sequenced from DNA isolated from the yeast clones. To express the nectin-4 antibodies recombinantly, the antibody variable heavy and light chain sequences were cloned upstream of the human heavy chain IgG1 and human light chain Igκ constant regions, respectively. Signal peptides were inserted upstream of the heavy and light chains to allow secretion of the antibodies. The complete anti-nectin-4 antibody human heavy chain and light chain cassettes were cloned downstream of the CMV promoter/enhancer in a cloning vector. A polyadenylation site was included downstream of the MAb coding sequence. The recombinant anti- nectin-4 antibody heavy and light chain expressing constructs were transfected into CHO cells. Stably transfected Chinese Hamster Ovary (CHO) cells underwent selection and recovery process for the generation of stable pools expressing recombinant antibodies and Fc variants. For the antibody generation, fed-batch production process with typical culture duration of 8 to 15 days was used for stably transfected pools prior to harvest of the culture media. Alternatively, transiently transfected cells were cultured for a typical duration of 3-15 days prior to harvest of the culture media. Subsequently, Protein-A affinity purification was performed for harvested cell culture fluid and purified materials were buffer exchanged into phosphate-buffered saline (PBS) or other preferred antibody formulation buffer. The quality of recombinant antibodies was assessed by size-exclusion chromatography, SDS-PAGE and other methods known in the art. The resulting NECTIN-4 antibodies are set forth in Table VI, Table VII and comprise (SEQ ID NO: 4) through (SEQ ID NO: 27). Example 2: Binding Assays of NECTIN-4 Antibodies. The binding affinity of NECTIN-4 antibodies of the invention were assessed using the following protocols. Briefly, Tumor cell lines were harvested, and cells re-suspended in FACS buffer (2% FBS + 5 mM EDTA in PBS). Cells were plated into 96-well round bottom plates and incubated with antibody (10 µg/mL) for one (1) hour on ice. For cell binding specificity determinations, antibodies were added at 10 µg/mL. After incubation, cells were pelleted by centrifugation at 200×g for 5 minutes, washed twice with FACS buffer, and counterstained with R-PE labeled goat anti-human Fc gamma fragment specific secondary antibody (Jackson Immuno Research; West Grove, PA) for an additional one (1) hour on ice, protected from light. Labeled cells were then washed twice with FACS buffer and analyzed by flow cytometry using an Attune NxT flow cytometer (Thermo Fisher Scientific; Carlsbad, CA). The results show that the NECTIN-4 antibodies bind specifically to NECTIN-4 on multiple cancer cell lines (T-47D, RT4, NCI-H1781, NCI-H322, PC-3, L-540, SU-DHL-1, and K562). (See, Figure(s) 1). Example 3: Binding Assays of NECTIN-4 Antibodies. In another example, the binding affinity of NECTIN-4 antibodies of the invention were assessed using the following protocols. Briefly, Tumor cell lines were harvested, and cells re-suspended in FACS buffer (2% FBS + 5 mM EDTA in PBS). Cells were plated into 96-well round bottom plates and incubated with antibody (10 µg/mL) for one (1) hour on ice. For cell binding specificity determinations, antibodies were added at 10 µg/mL with 3-fold dilutions. After incubation, cells were pelleted by centrifugation at 200×g for 5 minutes, washed twice with FACS buffer, and counterstained with R-PE labeled goat anti-human Fc gamma fragment specific secondary antibody (Jackson Immuno Research; West Grove, PA) for an additional one (1) hour on ice, protected from light. Labeled cells were then washed twice with FACS buffer and analyzed by flow cytometry using an Attune NxT flow cytometer (Thermo Fisher Scientific; Carlsbad, CA). The results show that the NECTIN-4 antibodies bind specifically to NECTIN-4 on T-47D breast cancer cell line. (See, Figure(s) 2 and Table XII). Example 4: Binding Assays of NECTIN-4 Antibodies. In another example, the binding affinity of NECTIN-4 antibodies of the invention were assessed using the following protocols. Briefly, Tumor cell lines were harvested, and cells re-suspended in FACS buffer (2% FBS + 5 mM EDTA in PBS). Cells were plated into 96-well round bottom plates and incubated with antibody (10 µg/mL) for one (1) hour on ice. For cell binding affinity determinations, antibodies were added at 10 µg/mL with 3-fold dilutions. After incubation, cells were pelleted by centrifugation at 200×g for 5 minutes, washed twice with FACS buffer, and counterstained with R-PE labeled goat anti-human Fc gamma fragment specific secondary antibody (Jackson Immuno Research; West Grove, PA) for an additional one (1) hour on ice, protected from light. Labeled cells were then washed twice with FACS buffer and analyzed by flow cytometry using an Attune NxT flow cytometer (Thermo Fisher Scientific; Carlsbad, CA). The results show that the NECTIN-4 antibodies bind specifically to NECTIN-4 on NCI-H292 lung cancer cell line and also bind comparatively to NCI-H292 in their respective ADC format. (See, Figure(s) 3 and Table XIII). Example 5: Cytotoxicity of NECTIN-4 ADCs In Vitro. The in vitro cytotoxicity of the NECTIN-4 ADCs was determined using the following protocols. Briefly, tumor cell lines were harvested, plated into 384-well white flat-bottom plates, and allowed to re- attach for 2-4 hours while incubating at 37°C. Cells were then treated with ADC or free payload test articles over a dose-titration (500 nM max with 5-fold dilutions). After 5-day treatment, the remaining cell viability was determined by CellTiter Glo assay based on the manufacturer’s instructions (Promega; Madison, WI). Data were normalized to non-treated control cells and dose-response curves were fitted using a 4-parameter logistic equation using GraphPad Prism software (version 9; La Jolla, CA). The results show that the NECTIN-4 ADCs have cytotoxic effects in vitro on multiple cancer cell lines, NECTIN-4 positive lung adenocarcinoma NCI-H322 cells (See, Figure(s) 4(A)), NECTIN-4 positive PC3-NECTIN-4 recombinant prostate cancer cells (See, Figure(s) 4(B)), but not on NECTIN-4- negative cells (See, Figure(s) 4(C)). See, also Table XIV. In another set of experiment(s) using the protocols set forth above, the in vitro cytotoxicity potencies (IC₅₀) are shown using the same NECTIN-4 Ab conjugated to nine (9) different linker / payloads. The IC₅₀ (nM) is set forth in Table XV. These results further affirm that the NECTIN-4 ADCs utilizing multiple linker / payloads have cytotoxic effects in vitro on the NECTIN-4 positive cell line PC3- NECTIN-4. Example 6: Cytotoxicity of NECTIN-4 ADC Payloads In Vitro. The in vitro cytotoxicity of the NECTIN-4 ADC payloads was determined using the following protocols. Briefly, tumor cell lines were harvested, plated into 384-well white flat-bottom plates, and allowed to re-attach for 2-4 hours while incubating at 37°C. Cells were then treated with ADC or free payload test articles over a dose-titration (500 nM max with 5-fold dilutions). After 5-day treatment, the remaining cell viability was determined by CellTiter Glo assay based on the manufacturer’s instructions (Promega; Madison, WI). Data were normalized to non-treated control cells and dose-response curves were fitted using a 4-parameter logistic equation using GraphPad Prism software (version 9; La Jolla, CA). The results show in vitro cytotoxicity of Nectin-4 ADCs displaying three (3) different payload entities (filled symbols) compared to the respective isotype control ADCs (open symbols) and respective free payloads (dotted lines) in the Nectin4-positive breast cancer cell line Sum190PT. (See, Figure(s) 5). Example 7: Bystander Activity of NECTIN-4 ADCs Compared to enfortumab vedotin. Bystander activity of the NECTIN-4 ADCs compared to commercial enfortumab vedotin (PADCEV) was determined using the following protocols. Briefly, using a co-culture model of Nectin-4 expressing PC3-Nectin4 recombinant cells and Nectin-4 non-expressing SU-DHL-1 cells labeled with Cell Trace Violet (Invitrogen; Waltham, MA) was conducted in 24-well plates. The ratio of target- positive to target-negative cells was 1:2. Following 96-hour treatment with ADC test articles, SU-DHL-1 cells were harvested and collected into 96-well round bottom plates and sequentially stained with Fixable Viability Dye (FVD) eFluor780 (Invitrogen) and APC-Annexin V (BioLegend; San Diego, CA) before analysis by flow cytometry. Monocultures of SU-DHL-1 cells treated with ADC served as controls to demonstrate non-target specific killing, or absence thereof. Early apoptotic (Annexin V single positive), late apoptotic (FVD eFluor780 single positive), and necrotic (Annexin V and FVD eFluor780 double positive) cells were considered non-viable. The results show bystander activity of a representative ADC (filled squares) compared to enfortumab vedotin (filled circles) and compared to no treatment (open triangle). Bystander activity is determined by graphing cell death of a Nectin4-negative cell line when co-cultured with a Nectin4- expressing cell line (Figure 6(A)). Non-specific activity of a representative ADC is absent compared to enfortumab vedotin in the target-negative cells mono-culture (Figure 6(B)). Example 8: Efficacy of NECTIN-4 ADCs Using Multiple Payloads in a HT1-376 Xenograft Model In Vivo. In vivo efficacy of the NECTIN-4 ADCs was performed using the following protocols. Briefly, HT-1376 cell suspension was mixed 1:1 with Matrigel.5,000,000 viable cells were subcutaneously injected into the rear flank of female BALB/c nude mice. When mean tumor size reached approximately 100 mm³, mice were randomized into five (5) groups. Test articles were dosed once at 5mg/kg. The study was terminated on day 28. The results show that all NECTIN-4 ADCs inhibited tumor growth when compared to the control groups. (See, Figure(s) 7). Example 9: Efficacy of NECTIN-4 ADC in a Sum190PT Breast Cancer Xenograft Model In Vivo. Further In vivo efficacy of a NECTIN-4 ADC (Ab5-ADC2) was performed using the following protocols. Briefly, Sum190PT cell suspension was mixed 1:1 with Cultrex ECM. 3,000,000 viable cells were subcutaneously injected into the rear flank of female NSG mice. When mean tumor size reached approximately 130 mm³, mice were randomized into groups, five (5) mice per group. Test articles were dosed at 10mg/kg twice one week apart. The study was terminated on day 28. The results show in vivo efficacy of a Nectin-4 ADC (filled circle) compared to the respective isotype control ADC (open square) and PBS group (open circle) in a Nectin4-positive Sum190PT breast cancer xenograft model. (See, Figure(s) 8). Example 10: Efficacy of NECTIN-4 ADC Compared to PADCEV in a Patient Derived Head and Neck Cancer Model In Vivo. Further In vivo efficacy of a NECTIN-4 ADC (Ab5-ADC2) compared to commercial enfortumab vedotin (PADCEV) was performed using the following protocols. Briefly, tumors derived from a head and neck squamous cell carcinoma patient were propagated in vivo in immunocompromised mice as a patient-derived xenograft (PDX). Tumor fragments (2-3mm in diameter) from stock mice were harvested and used for subcutaneous inoculation into female NOD/SCID mice. When mean tumor size reached approximately 150 mm³, mice were randomized into groups, five (5) mice per group. Test articles were dosed at 5 mg/kg or 10 mg/kg as single dose or twice, two (2) weeks apart. The results show Nectin-4 ADC (circles) displays better efficacy and complete tumor eradication compared to enfortumab vedotin (squares) in a Nectin4-positive patient-derived head and neck cancer model. (See, Figure(s) 9). Example 11: Use of Chimeric Antigen Receptor (CAR) T Cell Therapy in Cancers Expressing NECTIN-4. Generally speaking, T cells help find and fight off infections and diseases, such as cancer in the body. Many cancers can hide from T cells, thus when T cells cannot “see” cancer, the cancer may grow in the body. A promising form of immunotherapy in cancer is known as CAR-T therapy. In CAR-T therapy, a chimeric antigen receptor (CAR) is designed to recognize specific markers that are expressed in cancer (e.g., NECTIN-4). Studies have shown that when a CAR is attached to a specific antigen an immune response is induced and the T cells recognize cancer and can inhibit cancer growth. By way of a non-limiting example, blood is collected from a patient having cancer that expresses NECTIN-4. The T cells from the patient’s blood are isolated and genetically engineered to generate CAR-T cells. The CAR-T cells are cultivated and expanded using techniques known in the art. Finally, the CAR-T cells are infused into the patients’ bloodstream. See, JIN, et. al., Cancer Cell Int., 21:83 (2021). Trials initially demonstrate safety and thereafter confirm efficacy in repeat doses. Trials are open label comparing standard chemotherapy with standard therapy plus NECTIN-4 CAR-T cells. As will be appreciated, one non-limiting criteria that can be utilized in connection with enrollment of patients is concentration of NECTIN-4 in a tumor as determined by standard detection methods known in the art. Example 12: Use of Natural Killer (NK) Cell Therapy in Cancers Expressing NECTIN-4. Similar to CAR-T therapy, Natural Killer (NK) cell therapy is a form of immunotherapy that has shown promise in treating cancer (for example, cancers expressing NECTIN-4). Unlike T-cells, NK cells are not tailored to specific antigens. However, while NK cells can recognize and attack cancer cells, the NK cells do not live long enough or multiple quickly enough to fight cancer cells entirely. However, studies have shown that NK cells can be enhanced by treating them with immune system proteins called cytokines. Studies have shown that enhancing NK cells with cytokines allows for a more robust immune response. One advantage of NK cell therapy is the lack of side effects versus CAR-T therapy. In some instances, NK cells are also enhanced with CARs to make them more attuned to fighting cancer. See, LU, et. al., Frontiers in Oncology, vol.11, Art.720501 (Aug.2021). By way of a non-limiting example, several strategies can be used to enhance the efficacy of NK cell therapies. First, NK cells are generated from peripheral blood (PB), umbilical cord blood (UCB), induced pluripotent stem cells (iPSCs), and NK92 cell lines. After isolation from the aforementioned sources, NK cells are stimulated by cytokines such as IL-2, IL-15, and/or IL-18. Moreover, NK cells can be modified ex vivo to express CARs, allowing NK cells to recognize specific tumor associated antigens such as NECTIN-4. Finally, the NK cells are infused into the patients’ bloodstream. See, MEHTA, et. al., Int. J. of Hematology, 107:262-270 (2018). Trials initially demonstrate safety and thereafter confirm efficacy in repeat doses. Trials are open label comparing standard chemotherapy with standard therapy plus NECTIN-4 NK cells. As will be appreciated, one non-limiting criteria that can be utilized in connection with enrollment of patients is concentration of NECTIN-4 in a tumor as determined by standard detection methods known in the art. Example 13: NECTIN-4 antibodies and NECTIN-4 ADCs Characterization Assays. Nectin-4 antibodies and NECTIN-4 ADC compositions of the invention were further characterized using assays known in the art. The results shown in Figure 11 and Figure 12 confirm better safety profile and stronger efficacy, leading to an improved therapeutic window relative to other NECTIN-4 antibodies and NECTIN-4 ADCs known in the art. Example 14: Safety assessment of NECTIN-4 ADCs Across Multiple Primary Cultures of Human Normal Cells In Vitro. The in vitro cytotoxicity of the NECTIN-4 ADCs was determined using the following protocols. Briefly, normal human-derived primary cells including corneal epithelial cells, adult dermal fibroblasts and adult epidermal keratinocytes were harvested, plated into 384-well white flat-bottom plates, and allowed to re-attach for 2-4 hours while incubating at 37°C. Cells were then treated with ADC or free payload test articles over a dose-titration (1000 nM max with 5-fold dilutions). Then, after 5 or 6 day treatment, the cell viability was determined by a CellTiter Glo assay based on the manufacturer’s instructions (Promega; Madison, WI). Data were normalized to non-treated control cells and dose- response curves were fit using a 4-parameter logistic equation using GraphPad Prism software (version 9; La Jolla, CA). The results show that the NECTIN-4 ADC Ab5-ADC2 has significantly weaker cytotoxic effects in vitro than enfortumab vedotin on multiple normal primary cells, such as human corneal epithelial cells (See, Figure(s) 11(A)), adult dermal fibroblasts (See, Figure(s) 11(B)), and adult epidermal keratinocytes (See, Figure(s) 11(C)). See, also Table XVI, which shows the toxicokinetic parameters of ADC and total IgG at a repeat dose of up to 18 mg/kg and thus provides evidence of an increased HNSTD in NHP as an outcome of the described improved in vitro safety profile. In another set of experiment(s) using the protocols set forth above, the flow cytometry histograms of the aforementioned cells are shown. Human corneal epithelial cells (See, Figure(s) 12(A)), adult dermal fibroblasts (See, Figure(s) 12(B)), which show no NECTIN-4 expression and represent toxicity liabilities due to non-targeted ADC uptake, as well as adult epidermal keratinocytes (See, Figure(s) 12(C)), which express NECTIN-4 and represent on-target toxicity liabilities of NECTIN-4 ADCs. Example 15: Cell Cycle Analysis of Ab5-ADC2. In this experiment, the cell cycle analysis of Ab5-ADC2 was determined using the following protocols. Briefly, HT-1376 tumor cells were harvested and plated into 6-well plates and incubated overnight at 37°C. The next day, cells were treated with Ab5-ADC2 at 5 nM for 72 hours and then processed for propidium iodide staining with FxCycle PI/RNase Staining Solution (Invitrogen, Waltham, MA, USA). DNA content was measured by flow cytometry and cell cycle data modeling were analyzed using the Watson Pragmatic algorithm with FlowJo software (version 10; BD Biosciences, Franklin Lakes, NJ, USA). The results show the cell cycle analysis of the percent (%) combined G2 and sub-G1 phases of HT-1376 cells following 72-hour treatment with Ab5-ADC2. (See, Figure(s) 13(A)). Figure 13(B) shows representative flow cytometry histogram of Ab5-ADC2-treated cells that show increased cell populations in both sub-G1 and G2 phases of the cell cycle compared to non-treated control cells as expected for this payload class. Example 16: Immunogenic Cell Death (ICD) Analysis of Free Payload Compared to MMAE. In this experiment, the ICD analysis of Free Payload compared to MMAE was determined using the following protocols. Briefly, NCI-H292 tumor cells were harvested and plated into 100 mm culture dishes and incubated overnight at 37°C. The next day, cells were treated with free payload at 10 nM for 48 hours and then processed for live cell staining with immunogenic cell death (ICD) markers: anti- calreticulin, anti-HSP70 and anti-HMGB1. All marker antibodies were labeled with AlexaFluor 488 (Novus Biologicals, Centennial, CO, USA). Cells were analyzed by flow cytometry using an Attune NxT flow cytometer and % ICD marker positivity was determined relative to isotype control antibody staining. The results show an increase in markers of immunogenic cell death to similar extent with both payloads as expected for this payload class. (See, Figure(s) 14)). Example 17: Complement Dependent Cytotoxicity (CDC) Analysis of Ab5-ADC2 and Ab5. In this experiment, the CDC analysis of Ab5-ADC2 was determined using the following protocols. Briefly, HT-1376 tumor cells were harvested and plated into 96-well white flat-bottom plates and incubated with indicated serially diluted test articles for one (1) hour on ice to allow binding of antibody or ADC to cells. Cells were then opsonized with baby rabbit complement for 1 hour at 37°C, and remaining cell viability following cell lysis due to CDC activity was determined by CellTiter-Glo 2.0 Assay (Promega). The results show lack of any significant CDC activity for Ab5-ADC2 as well as enfortumab. (See, Figure(s) 15)). Example 18: Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Analysis of Ab5-ADC2 and Ab5. In this experiment, the ADCC analysis of Ab5-ADC2 was determined using the following protocols. Briefly, NCI-H292 tumor cells were harvested and plated into 96-well white flat-bottom plates and incubated overnight at 37°C. The next day, tumor cells were co-incubated with engineered effector cells (6:1 ratio of effector to target cells) in the presence of indicated antibody or ADC test articles for 6 hours, and ADCC activity was measured using a commercial ADCC Reporter Bioassay, V Variant kit (Promega, Madison, WI, USA). The results show that while the positive control (Her2 Ab) showed strong ADCC activity, no significant ADCC activity was observed for Ab5-ADC2. (See, Figure(s) 16)). Example 19: Antibody-Dependent Cell-Mediated Phagocytosis (ADCP) Analysis of Ab5-ADC2 and Ab5. In this experiment, the ADCP analysis of Ab5-ADC2 was determined using the following protocols. Briefly, Tumor cells were harvested and plated into 384-well white flat-bottom plates and incubated overnight at 37°C. The next day, tumor cells were co-incubated with engineered effector cells (6:1 to 7.5:1 ratio of effector to target cells) in the presence of indicated antibody or ADC test articles for 6 hours, and ADCP activity was measured using commercial FcγRI ADCP bioassay kit (Promega). The results show that compared to the assay control reagent (isoCTRL Ab in RAMOS cells expressing the target of the isoCTRL Ab) weak ADCP activity was observed for Ab5-ADC2 in the NECTIN-4 expressing SUM190PT and HT-1376 cancer cell lines. (See, Figure(s) 17)). Overall, lack of CDC, ADCC and ADCP findings rule out any significant contribution of FcR- mediated effector function activity to the mechanism of action of Ab5-ADC2. Example 20: Pharmacokinetics Profile of ADC and Free Payload of Ab5-ADC2 in Cynomolgus Monkeys. In this experiment, the pharmacokinetics profile of Ab5-ADC2 and its corresponding free payload was determined using the following protocols. Briefly, Cynomolgus monkeys were dosed with ADC test article Ab5-ADC2 at different doses levels for 2 doses. Blood was collected at different timepoints and processed into serum for total antibody and ADC quantitation, and plasma for free payload analysis. Enzyme-linked immunosorbent assay (ELISA) was used to quantitate the total antibody and ADC concentrations by capturing with soluble recombinant NECTIN-4 and detecting with either biotin-labelled anti-human IgG, or biotin-labelled anti-payload, respectively, followed by binding of “Streptavidin-HRP”. TMB was used as the colorimetric substrate, and the color reaction was stopped by H2SO4 solution. The absorbance was measured at 450 nm-630 nm on a plate reader. The calibration curve was generated by plotting the response (the mean absorbance of each calibration curve sample minus the mean absorbance value of blank) of serially diluted test article against the calibration sample concentrations and fitting by a four-parameter logistic model. All data were analyzed by the SoftMax Pro 7.0 software. For the free payload quantitation, payload was extracted from 20 μL cynomolgus monkey K2EDTA plasma by protein precipitation, then detected and quantified by AB SCIEX TRIPLE QUAD^TM 6500+ mass spectrometer, using an internal standard. TK parameters are summarized in Table XVI. The results show a linear PK profile for total IgG, ADC, and free payload without significant accumulation. Notably, total IgG and ADC curves are overlapping at each dose level and throughout the time course of the 21-day dosing cycle with a half-life of about 5 days (Table XVI.), which is achieved through the very stable conjugation technology used to generate Ab5-ADC2. Importantly, a repeat dosing of 18 mg/kg of Ab5-ADC2 was well-tolerated in non-human primates, which is achieved through the increase in conjugation stability and better tumor-targeted payload accumulation while sparing normal tissues (See, Figure(s) 18)). Example 21: Efficacy of NECTIN-4 ADC Compared to Enfortumab Vedotin in a Patient Derived Cervical Cancer Model PDX36 In Vivo. Further In vivo efficacy of a NECTIN-4 ADC (Ab5-ADC2) compared to commercial Enfortumab Vedotin was performed using the following protocols. Briefly, PDX (in this instance PDX36) derived from patients with cervical cancer were propagated in vivo in immunocompromised mice. Tumor fragments (2-3mm in diameter) from stock mice were harvested and used for subcutaneous inoculation into female NOD/SCID mice. When mean tumor size reached approximately 150 mm³, mice were randomized into groups, 5 mice per group. Test articles were dosed at 2.5, 5 or 10mg/kg. The results show Ab5-ADC2 (dark circles) display better efficacy and tumor inhibition compared to Enfortumab Vedotin (dark triangles) in a patient-derived cervical cancer model, which translates to longer on-study survival of tumor-bearing mice treated with Ab5-ADC2. (See, Figures 19(A) and 19(B)). Example 22: Efficacy of NECTIN-4 ADC in Multiple Patient Derived Cervical Cancer Models (PDX10, PDX12, PDX13, PDX16, PDX34, and PDX36) In Vivo. Further In vivo efficacy of NECTIN-4 ADC (Ab5-ADC2) was performed in multiple cervical cancer model(s) using the following protocols. Briefly, PDX (in this instance PDX10, PDX12, PDX13, PDX16, PDX34, and PDX36) derived from patients with cervical cancer were propagated in vivo in immunocompromised mice. Tumor fragments (2-3mm in diameter) from stock mice were harvested and used for subcutaneous inoculation into female NOD/SCID mice. When mean tumor size reached approximately 150 mm³, mice were randomized into groups, 5 mice per group. Test articles were dosed at 2.5, 5 or 10mg/kg. The results show Ab5-ADC2 (dark circles) display significant efficacy and tumor inhibition compared to vehicle control in multiple patient-derived cervical cancer model. (See, Figure(s) 20(A) – 20(F)). Example 23: NECTIN-4 Expression in Patient-Derived Cervical Cancer Models via Immunohistochemistry. Expression characterization of the NECTIN-4 patient-derived cervical cancer xenograft models was assessed using the following protocols. Briefly, the tissue samples were fixed in 10% buffered neutral formalin, processed, and embedded into paraffin wax, then prepared as 4 µm tissue sections. After deparaffinization and re-hydration, sections were treated for antigen retrieval. The tissue sections after antigen retrieval were then incubated with mouse anti-nectin-4 primary antibody or IgG (antibody control). The tissue sections bound with primary antibodies were washed and detected with an enzyme-labeled, secondary antibody. The bound secondary antibody was color-developed, using the Leica Bond Refine Polymer Detection system. The stained tissue sections were then scanned, imaged, and evaluated with light microscopy, using an Aperio ScanScope CS (Aperio; Vista, CA). All stained sections were scanned using a NanoZoomer-HT 2.0 Image system using 40x magnification and images generated. The results show expression of NECTIN-4 was confirmed by IHC using an anti-Nectin-4 antibody. The PDX12 (21(A) and 21(B)), PDX10 (21(C) and 21(D)), PDX16 (21(E) and 21(F)), PDX13 (21(G) and 21(H)), PDX34 (21(I) and 21(J)), and PDX36 (21(K) and 21(L)) are shown in the respective figures with images shown at high resolution (21(A), (C), (E), (G), (I) and (K)), as well as at low resolution (21(B), (D), (F), (H), (J) and (L)). (See, Figure(s) 21). These PDX models show a range of NECTIN-4 expression patterns, including PDX models with very heterogenous NECTIN-4 expression. Nevertheless, Ab5-ADC2 was able to achieve significant tumor growth inhibition in all models. Example 24: Free Payload Concentration Analysis of Ab5-ADC2 or Enfortumab Vedotin via LC- MS/MS. Free payload concentration of Ab5-ADC2 or Enfortumab Vedotin in multiple tissues of NECTIN- 4 positive breast cancer tumor bearing mice was assessed using the following protocols. Briefly, a Sum190PT inflammatory breast cancer xenograft mouse model was dosed with either Ab5-ADC2 or Enfortumab Vedotin. Tumor, normal tissues, and plasma were collected and analyzed for payload concentration by LC-MS/MS. The results in Figure 22(A) show free payload concentration versus MMAE. The results in Figure 22(B) show payload concentration of Ab5-ADC2 versus Enfortumab Vedotin. Notably, Ab5- ADC2 is able to deliver more payload to NECTIN-4 expressing tumors, while decreasing payload exposure in normal tissues, which is the basis of the better safety profile compared to enfortumab vedotin. Example 25: Stability and DAR Retention Analysis Ab5-ADC2. Stability assessment and DAR retention analysis were performed using the following protocols. Briefly, Sprague Dawley rats, 10-12 weeks old upon arrival, were acclimated for one week and then given a single intravenous dose of Ab5-ADC2 or Enfortumab Vedotin. Blood samples were collected post-dose at various timepoints: 1 hour, 4 hours, day 3, 7, 14 and 21 days. Blood collected in EDTA coated tubes was processed to plasma by centrifuging at 10,000g for 10 minutes at 4°C. Plasma was aliquoted and stored frozen at -80°C until analysis. Plasma samples were diluted in TBS then combined with biotin-labelled capture anti-human antibody coated beads, followed by mixing with streptavidin coated DynaBeads (Invitrogen) and incubated for about 2 hours. The affinity captured ADC on beads was subjected to a magnet to collect the complex, then washed and the ADC. Affinity purified ADC was run on an Agilent QTOF 6550 B under MassHunter B.07.00 or equivalent. The peaks were integrated, extracted and spectra deconvoluted using the Maximum Entropy algorithm. The deconvoluted spectra was exported as CSV file and imported in DAR Calculator. The DAR was determined for each sample and plotted over time. The results in Figure 23(A) show stability of the conjugation and drug-to-antibody ratio (DAR) of Ab5-ADC2 compared to Enfortumab Vedotin over time after iv injection. The results in Figure 23(B) show the deconvoluted MS profiles of the heavy and light chains of affinity purified Ab5-ADC2 from the plasma after 1 hour and 21 days from injection in Sprague Dawley rats. Taken together, these results indicate that Ab5-ADC2 is very stable in circulation, which allows for an increase in payload delivery to tumor over normal tissue as demonstrated in Figure 22. Importantly, this enables an HNSTD (highest non-severely toxic dose) dose of 18 mg/kg in non-human primates as shown in Figure 18. Example 26: Human Clinical Trials for the Treatment of Human Carcinomas through the Use of NECTIN-4 antibodies and NECTIN-4 ADCs. NECTIN-4 antibodies and NECTIN-4 ADCs are synthesized in accordance with the present invention which specifically accumulate in a tumor cell and are used in the treatment of certain tumors and other immunological disorders and/or other diseases (See, Table I). In connection with each of these indications, two clinical approaches are successfully pursued. I.) Adjunctive therapy: In adjunctive therapy, patients are treated with NECTIN-4 antibodies and NECTIN-4 ADCs in combination with a chemotherapeutic or pharmaceutical or biopharmaceutical agent or a combination thereof. Primary cancer targets are treated under standard protocols by the addition of NECTIN-4 antibodies and NECTIN-4 ADCs. Protocol designs address effectiveness as assessed by the following examples, including but not limited to, reduction in tumor mass of primary or metastatic lesions, increased progression free survival, overall survival, improvement of patient’s health, disease stabilization, as well as the ability to reduce usual doses of standard chemotherapy and other biologic agents. These dosage reductions allow additional and/or prolonged therapy by reducing dose-related toxicity of the chemotherapeutic or biologic agent. II.) Monotherapy: In connection with the use of the NECTIN-4 antibodies and NECTIN-4 ADCs in monotherapy of tumors, the NECTIN-4 antibodies and NECTIN-4 ADCs are administered to patients without a chemotherapeutic or pharmaceutical or biological agent. In one embodiment, monotherapy is conducted clinically in end-stage cancer patients with extensive metastatic disease. Protocol designs address effectiveness as assessed by the following examples, including but not limited to, reduction in tumor mass of primary or metastatic lesions, increased progression free survival, overall survival, improvement of patient’s health, disease stabilization, as well as the ability to reduce usual doses of standard chemotherapy and other biologic agents. Dosage Dosage regimens may be adjusted to provide the optimum desired response. For example, a single NECTIN-4 antibodie(s) and NECTIN-4 ADC injection may be administered, several divided doses may be administered over time, or the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. “Dosage Unit Form” as used herein refers to physically discrete units suited as unitary dosages for the mammalian subjects to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on (a) the unique characteristics of the NECTIN-4 antibodie(s) and NECTIN-4 ADC, the individual mechanics of the irradiation mechanism (reactor) and the particular therapeutic or prophylactic effect to be achieved, and (b) the limitations inherent in the art of compounding such an compound for the treatment of sensitivity in individuals. Clinical Development Plan (CDP) The CDP follows and develops treatments of cancer(s) and/or immunological disorders (See, Table I) using NECTIN-4 antibodies and NECTIN-4 ADCs of the disclosure. Trials initially demonstrate safety and thereafter confirm efficacy in repeat doses. Trials are open label comparing standard chemotherapy with standard therapy plus NECTIN-4 antibodie(s) and NECTIN-4 ADCs. As will be appreciated, one non-limiting criteria that can be utilized in connection with enrollment of patients is concentration of NECTIN-4 antibodie(s) and NECTIN-4 ADCs in a tumor as determined by standard detection methods known in the art. The present invention is not to be limited in scope by the embodiments disclosed herein, which are intended as single illustrations of individual aspects of the invention, and any that are functionally equivalent are within the scope of the invention. Various modifications to the models, methods, and life cycle methodology of the invention, in addition to those described herein, will become apparent to those skilled in the art from the foregoing description and teachings, and are similarly intended to fall within the scope of the invention. Such modifications or other embodiments can be practiced without departing from the true scope and spirit of the invention.

Table I. Representative List of Cancer(s) to be Treated. # Cancers 1 Bl 2 En 3 He 4 Lu 5 Ov 6 Pa 7 Ce 8 Br 9 Es 10 Pr 11 Ga 12 Co 13 Br 14 Bo 15 Sk 16 Liv 17 Ki

Table II. Amino Acid Abbreviations.

Table III. Amino Acid Substitution Matrix.

Table IV. Nucleic acid sequence (SEQ ID NO: 1) and amino acid sequence (SEQ ID NO: 2) of human nectin cell adhesion molecule 4 (NECTIN-4). 1 - ATGCCCCTGTCCCTGGGAGCCGAGATGTGGGGGCCTGAGGCCTGGCTGCTGCTGCTGCTA - 60 1 - M P L S L G A E M W G P E A W L L L L L - 20 61 - CTGCTGGCATCATTTACAGGCCGGTGCCCCGCGGGTGAGCTGGAGACCTCAGACGTGGTA - 120 21 - L L A S F T G R C P A G E L E T S D V V - 40 121 - ACTGTGGTGCTGGGCCAGGACGCAAAACTGCCCTGCTTCTACCGAGGGGACTCCGGCGAG - 180 41 - T V V L G Q D A K L P C F Y R G D S G E - 60 181 - CAAGTGGGGCAAGTGGCATGGGCTCGGGTGGACGCGGGCGAAGGCGCCCAGGAACTAGCG - 240 61 - Q V G Q V A W A R V D A G E G A Q E L A - 80 241 - CTACTGCACTCCAAATACGGGCTTCATGTGAGCCCGGCTTACGAGGGCCGCGTGGAGCAG - 300 81 - L L H S K Y G L H V S P A Y E G R V E Q - 100 301 - CCGCCGCCCCCACGCAACCCCCTGGACGGCTCAGTGCTCCTGCGCAACGCAGTGCAGGCG - 360 101 - P P P P R N P L D G S V L L R N A V Q A - 120 361 - GATGAGGGCGAGTACGAGTGCCGGGTCAGCACCTTCCCCGCCGGCAGCTTCCAGGCGCGG - 420 121 - D E G E Y E C R V S T F P A G S F Q A R - 140 421 - CTGCGGCTCCGAGTGCTGGTGCCTCCCCTGCCCTCACTGAATCCTGGTCCAGCACTAGAA - 480 141 - L R L R V L V P P L P S L N P G P A L E - 160 481 - GAGGGCCAGGGCCTGACCCTGGCAGCCTCCTGCACAGCTGAGGGCAGCCCAGCCCCCAGC - 540 161 - E G Q G L T L A A S C T A E G S P A P S - 180 541 - GTGACCTGGGACACGGAGGTCAAAGGCACAACGTCCAGCCGTTCCTTCAAGCACTCCCGC - 600 181 - V T W D T E V K G T T S S R S F K H S R - 200 601 - TCTGCTGCCGTCACCTCAGAGTTCCACTTGGTGCCTAGCCGCAGCATGAATGGGCAGCCA - 660 201 - S A A V T S E F H L V P S R S M N G Q P - 220 661 - CTGACTTGTGTGGTGTCCCATCCTGGCCTGCTCCAGGACCAAAGGATCACCCACATCCTC - 720 221 - L T C V V S H P G L L Q D Q R I T H I L - 240 721 - CACGTGTCCTTCCTTGCTGAGGCCTCTGTGAGGGGCCTTGAAGACCAAAATCTGTGGCAC - 780 241 - H V S F L A E A S V R G L E D Q N L W H - 260 781 - ATTGGCAGAGAAGGAGCTATGCTCAAGTGCCTGAGTGAAGGGCAGCCCCCTCCCTCATAC - 840 261 - I G R E G A M L K C L S E G Q P P P S Y - 280 841 - AACTGGACACGGCTGGATGGGCCTCTGCCCAGTGGGGTACGAGTGGATGGGGACACTTTG - 900 281 - N W T R L D G P L P S G V R V D G D T L - 300 901 - GGCTTTCCCCCACTGACCACTGAGCACAGCGGCATCTACGTCTGCCATGTCAGCAATGAG - 960 301 - G F P P L T T E H S G I Y V C H V S N E - 320 961 - TTCTCCTCAAGGGATTCTCAGGTCACTGTGGATGTTCTTGACCCCCAGGAAGACTCTGGG -1020 321 - F S S R D S Q V T V D V L D P Q E D S G - 340 1021 - AAGCAGGTGGACCTAGTGTCAGCCTCGGTGGTGGTGGTGGGTGTGATCGCCGCACTCTTG -1080 341 - K Q V D L V S A S V V V V G V I A A L L - 360 1081 - TTCTGCCTTCTGGTGGTGGTGGTGGTGCTCATGTCCCGATACCATCGGCGCAAGGCCCAG -1140 361 - F C L L V V V V V L M S R Y H R R K A Q - 380 1141 - CAGATGACCCAGAAATATGAGGAGGAGCTGACCCTGACCAGGGAGAACTCCATCCGGAGG -1200 381 - Q M T Q K Y E E E L T L T R E N S I R R - 400 1201 - CTGCATTCCCATCACACGGACCCCAGGAGCCAGCCGGAGGAGAGTGTAGGGCTGAGAGCC -1260 401 - L H S H H T D P R S Q P E E S V G L R A - 420 1261 - GAGGGCCACCCTGATAGTCTCAAGGACAACAGTAGCTGCTCTGTGATGAGTGAAGAGCCC -1320 421 - E G H P D S L K D N S S C S V M S E E P - 440 1321 - GAGGGCCGCAGTTACTCCACGCTGACCACGGTGAGGGAGATAGAAACACAGACTGAACTG -1380 441 - E G R S Y S T L T T V R E I E T Q T E L - 460 1381 - CTGTCTCCAGGCTCTGGGCGGGCCGAGGAGGAGGAAGATCAGGATGAAGGCATCAAACAG -1440 461 - L S P G S G R A E E E E D Q D E G I K Q - 480 1441 - GCCATGAACCATTTTGTTCAGGAGAATGGGACCCTACGGGCCAAGCCCACGGGCAATGGC -1500 481 - A M N H F V Q E N G T L R A K P T G N G - 500 1501 - ATCTACATCAATGGGCGGGGACACCTGGTCTGA - 1533 501 - I Y I N G R G H L V * - 520 Table V. Amino acid sequence (SEQ ID NO: 3) of the human nectin cell adhesion molecule 4 (NECTIN-4). Signal peptide is underlined. MPLSLGAEMWGPEAWLLLLLLLASFTGRCPAGELETSDVVTVVLGQDAKLPCFYRGDSGEQVGQVAWA RVDAGEGAQELALLHSKYGLHVSPAYEGRVEQPPPPRNPLDGSVLLRNAVQADEGEYECRVSTFPAGS FQARLRLRVLVPPLPSLNPGPALEEGQGLTLAASCTAEGSPAPSVTWDTEVKGTTSSRSFKHSRSAAV TSEFHLVPSRSMNGQPLTCVVSHPGLLQDQRITHILHVSFLAEASVRGLEDQNLWHIGREGAMLKCLS EGQPPPSYNWTRLDGPLPSGVRVDGDTLGFPPLTTEHSGIYVCHVSNEFSSRDSQVTVDVLDPQEDSG KQVDLVSASVVVVGVIAALLFCLLVVVVVLMSRYHRRKAQQMTQKYEEELTLTRENSIRRLHSHHTDP RSQPEESVGLRAEGHPDSLKDNSSCSVMSEEPEGRSYSTLTTVREIETQTELLSPGSGRAEEEEDQDE GIKQAMNHFVQENGTLRAKPTGNGIYINGRGHLV*

Table(s) VI(A) thru VI(F). Sequences of Antibody Heavy Chains. Table VI(A). The cDNA sequence (SEQ ID NO: 4) and amino acid sequence (SEQ ID NO: 5) of CL.Z heavy chain. The nucleotide sequence encoding the variable region is underlined. 1 – CAGGTTCAGTTAGTCGAGTCTGGTGGCGGTGTCGTCCAGCCTGGTAGATCCTTAAGGCTG – 60 1 - Q V Q L V E S G G G V V Q P G R S L R L - 20 61 – TCATGTGCCGCTAGCGGATTTTCTTTTTCTGCTTACGGTATGCATTGGGTGAGACAAGCC – 120

241 – CTGCAGATGAACTCATTGAGAGCTGAGGACACCGCAGTGTATTACTGTGCTAGAGGTGTT – 300 81 - L Q M N S L R A E D T A V Y Y C A R G V - 100 301 – GGTGCTTTTCCATGGGTTTTTTTTGATTACTGGGGACAAGGAACTTTGGTCACAGTGTCA – 360 101 - G A F P W V F F D Y W G Q G T L V T V S - 120 361 – TCTGCCAGCACTAAAGGGCCCTCTGTGTTCCCTCTGGCCCCCAGCAGCAAGAGCACATCT – 420 121 - S A S T K G P S V F P L A P S S K S T S - 140 421 – GGCGGAACAGCCGCCCTGGGCTGCCTGGTGAAAGACTACTTCCCCGAGCCCGTGACCGTG – 480 141 - G G T A A L G C L V K D Y F P E P V T V - 160 481 – TCCTGGAACTCTGGCGCCCTGACCAGCGGCGTGCACACCTTTCCAGCCGTGCTGCAGAGC – 540 161 - S W N S G A L T S G V H T F P A V L Q S - 180 541 – AGCGGCCTGTACAGCCTGAGCAGCGTGGTGACAGTGCCCAGCAGCAGCCTGGGCACCCAG – 600 181 - S G L Y S L S S V V T V P S S S L G T Q - 200 601 – ACCTACATCTGCAACGTGAACCACAAGCCCAGCAACACCAAGGTGGACAAGAAGGTGGAA – 660 201 - T Y I C N V N H K P S N T K V D K K V E - 220 661 – CCCAAGAGCTGCGACAAGACCCACACCTGTCCCCCCTGCCCTGCCCCTGAACTGCTGGGC – 720 221 - P K S C D K T H T C P P C P A P E L L G - 240 721 – GGACCCAGCGTGTTCCTGTTCCCGCCGAAACCGAAAGATACCCTGATGATTAGCCGCACC – 780 241 - G P S V F L F P P K P K D T L M I S R T - 260 781 – CCGGAAGTGACCTGCGTGGTGGTGGATGTGAGCCATGAAGATCCGGAAGTGAAATTTAAC – 840 261 - P E V T C V V V D V S H E D P E V K F N - 280 841 – TGGTATGTGGATGGCGTGGAAGTGCATAACGCGAAAACCAAACCGCGCGAAGAACAGTAT – 900 281 - W Y V D G V E V H N A K T K P R E E Q Y - 300 901 – AACAGCACCTATCGCGTGGTGAGCGTGCTGACCGTGCTGCATCAGGATTGGCTGAACGGC – 960 301 - N S T Y R V V S V L T V L H Q D W L N G - 320 961 – AAAGAATATAAATGCAAAGTGAGCAACAAAGCGCTGCCGGCGCCGATTGAAAAAACCATT -1020 321 - K E Y K C K V S N K A L P A P I E K T I - 340 1021 – AGCAAAGCGAAAGGCCAGCCGCGCGAACCGCAGGTGTATACCCTGCCGCCGAGCCGCGAA -1080 341 - S K A K G Q P R E P Q V Y T L P P S R E - 360 1081 – GAAATGACCAAAAACCAGGTGAGCCTGACCTGCCTGGTGAAAGGCTTTTATCCGAGCGAT -1140 361 - E M T K N Q V S L T C L V K G F Y P S D - 380 1141 – ATTGCGGTGGAATGGGAAAGCAACGGCCAGCCGGAAAACAACTATAAAACCACCCCGCCG -1200 381 - I A V E W E S N G Q P E N N Y K T T P P - 400 1201 – GTGCTGGATAGCGATGGCAGCTTTTTTCTGTATAGCAAACTGACCGTGGATAAAAGCCGC -1260 401 - V L D S D G S F F L Y S K L T V D K S R - 420 1261 – TGGCAGCAGGGCAACGTGTTTAGCTGCAGCGTGATGCATGAAGCGCTGCATAACCATTAT -1320 421 - W Q Q G N V F S C S V M H E A L H N H Y - 440 1321 – ACCCAGAAAAGCCTGAGCCTGAGCCCGGGCAAATGA – 1356 441 - T Q K S L S L S P G K * - 451 Table VI(B). The cDNA sequence (SEQ ID NO: 6) and amino acid sequence (SEQ ID NO: 7) of CL.X heavy chain. The nucleotide sequence encoding the variable region is underlined. 1 – CAGGTCCAGTTAGTTCAATCAGGTGCCGAGGTCAAAAAGCCAGGTTCTTCCGTCAAAGTG – 60 1 - Q V Q L V Q S G A E V K K P G S S V K V - 20 61 – TCATGCAAGGCTAGCGGTGGCACCTTTTCTTCTTACGCTTTTTCTTGGGTGAGACAGGCA – 120 21 - S C K A S G G T F S S W V R Q A - 40 121 – – 180 41 - P G Q G L E W M G R F G T T N Y - 60 181 – – 240 61 - A Q K F Q G R V T I

S T S T A Y - 80 241 – ATGGAATTAAGTTCTCTGAGATCCGAGGACACCGCAGTGTATTACTGTGCTAGACAGGCT – 300 81 - M E L S S L R S E D T A V Y Y C A R Q A - 100 301 – GGTGGTGTTCTGGATGTTTGGGGACAAGGAACTTTGGTCACAGTGTCATCTGCCAGCACT – 360 101 - G G V L D V W G Q G T L V T V S S A S T - 120 361 – AAAGGGCCCTCTGTGTTCCCTCTGGCCCCCAGCAGCAAGAGCACATCTGGCGGAACAGCC – 420 121 - K G P S V F P L A P S S K S T S G G T A - 140 421 – GCCCTGGGCTGCCTGGTGAAAGACTACTTCCCCGAGCCCGTGACCGTGTCCTGGAACTCT – 480 141 - A L G C L V K D Y F P E P V T V S W N S - 160 481 – GGCGCCCTGACCAGCGGCGTGCACACCTTTCCAGCCGTGCTGCAGAGCAGCGGCCTGTAC – 540 161 - G A L T S G V H T F P A V L Q S S G L Y - 180 541 – AGCCTGAGCAGCGTGGTGACAGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGC – 600 181 - S L S S V V T V P S S S L G T Q T Y I C - 200 601 – AACGTGAACCACAAGCCCAGCAACACCAAGGTGGACAAGAAGGTGGAACCCAAGAGCTGC – 660 201 - N V N H K P S N T K V D K K V E P K S C - 220 661 – GACAAGACCCACACCTGTCCCCCCTGCCCTGCCCCTGAACTGCTGGGCGGACCCAGCGTG – 720 221 - D K T H T C P P C P A P E L L G G P S V - 240 721 – TTCCTGTTCCCGCCGAAACCGAAAGATACCCTGATGATTAGCCGCACCCCGGAAGTGACC – 780 P E V T - 260 – 840

W Y V D - 280 841 – GGCGTGGAAGTGCATAACGCGAAAACCAAACCGCGCGAAGAACAGTATAACAGCACCTAT – 900 281 - G V E V H N A K T K P R E E Q Y N S T Y - 300 901 – CGCGTGGTGAGCGTGCTGACCGTGCTGCATCAGGATTGGCTGAACGGCAAAGAATATAAA – 960 301 - R V V S V L T V L H Q D W L N G K E Y K - 320 961 – TGCAAAGTGAGCAACAAAGCGCTGCCGGCGCCGATTGAAAAAACCATTAGCAAAGCGAAA -1020 321 - C K V S N K A L P A P I E K T I S K A K - 340 1021 – GGCCAGCCGCGCGAACCGCAGGTGTATACCCTGCCGCCGAGCCGCGAAGAAATGACCAAA -1080 341 - G Q P R E P Q V Y T L P P S R E E M T K - 360 1081 – AACCAGGTGAGCCTGACCTGCCTGGTGAAAGGCTTTTATCCGAGCGATATTGCGGTGGAA -1140 361 - N Q V S L T C L V K G F Y P S D I A V E - 380 1141 – TGGGAAAGCAACGGCCAGCCGGAAAACAACTATAAAACCACCCCGCCGGTGCTGGATAGC -1200 381 - W E S N G Q P E N N Y K T T P P V L D S - 400 1201 – GATGGCAGCTTTTTTCTGTATAGCAAACTGACCGTGGATAAAAGCCGCTGGCAGCAGGGC -1260 401 - D G S F F L Y S K L T V D K S R W Q Q G - 420 1261 – AACGTGTTTAGCTGCAGCGTGATGCATGAAGCGCTGCATAACCATTATACCCAGAAAAGC -1320 421 - N V F S C S V M H E A L H N H Y T Q K S - 440 1321 – CTGAGCCTGAGCCCGGGCAAATGA – 1344 441 - L S L S P G K * - 447 Table VI(C). The cDNA sequence (SEQ ID NO: 8) and amino acid sequence (SEQ ID NO: 9) of CL.N heavy chain. The nucleotide sequence encoding the variable region is underlined. 1 - CAGGTTCAGTTAGTCGAGTCTGGTGGCGGTGTCGTCCAGCCTGGTAGATCCTTAAGGCTG - 60 1 - Q V Q L V E S G G G V V Q P G R S L R L - 20 61 - TCATGTGCCGCTAGCGGATTTACCTTTGGTGGTTACGGTATGCATTGGGTGAGACAAGCC - 120 21 - S C A A S G F T F G G Y G M H W V R Q A - 40 121 - CCCGGTAAAGGCCTGGAATGGGTCGCTGTGATAAGTTACTCTGGTTCTAACAAATACTAC - 180

661 - GAACCCAAGAGCTGCGACAAGACCCACACCTGTCCCCCCTGCCCTGCCCCTGAACTGCTG - 720 221 - E P K S C D K T H T C P P C P A P E L L - 240 721 - GGCGGACCCAGCGTGTTCCTGTTCCCGCCGAAACCGAAAGATACCCTGATGATTAGCCGC - 780 241 - G G P S V F L F P P K P K D T L M I S R - 260 781 - ACCCCGGAAGTGACCTGCGTGGTGGTGGATGTGAGCCATGAAGATCCGGAAGTGAAATTT - 840 261 - T P E V T C V V V D V S H E D P E V K F - 280 841 - AACTGGTATGTGGATGGCGTGGAAGTGCATAACGCGAAAACCAAACCGCGCGAAGAACAG - 900 281 - N W Y V D G V E V H N A K T K P R E E Q - 300 901 - TATAACAGCACCTATCGCGTGGTGAGCGTGCTGACCGTGCTGCATCAGGATTGGCTGAAC - 960 301 - Y N S T Y R V V S V L T V L H Q D W L N - 320 961 - GGCAAAGAATATAAATGCAAAGTGAGCAACAAAGCGCTGCCGGCGCCGATTGAAAAAACC -1020 K C K V S N K A L P A P I E K T - 340 -1080 K G Q P R E P Q V Y T L P P S R - 360 -1140 K N Q V S L T C L V K G F Y P S - 380 -1200

E W E S N G Q P E N N Y K T T P - 400 1201 - CCGGTGCTGGATAGCGATGGCAGCTTTTTTCTGTATAGCAAACTGACCGTGGATAAAAGC -1260 401 - P V L D S D G S F F L Y S K L T V D K S - 420 1261 - CGCTGGCAGCAGGGCAACGTGTTTAGCTGCAGCGTGATGCATGAAGCGCTGCATAACCAT -1320 421 - R W Q Q G N V F S C S V M H E A L H N H - 440 1321 - TATACCCAGAAAAGCCTGAGCCTGAGCCCGGGCAAATGA - 1359 441 - Y T Q K S L S L S P G K * - 452 Table VI(D). The cDNA sequence (SEQ ID NO: 10) and amino acid sequence (SEQ ID NO: 11) of CL.I heavy chain. The nucleotide sequence encoding the variable region is underlined.

241 - CTGCAGATGAACTCATTGAGAGCTGAGGACACCGCAGTGTATTACTGTGCTAGAAGACAT - 300 81 - L Q M N S L R A E D T A V Y Y C A R R H - 100 301 - TACTCTTACGGTTTTGATGTTTGGGGACAAGGAACTTTGGTCACAGTGTCATCTGCCAGC - 360 101 - Y S Y G F D V W G Q G T L V T V S S A S - 120 361 - ACTAAAGGGCCCTCTGTGTTCCCTCTGGCCCCCAGCAGCAAGAGCACATCTGGCGGAACA - 420 121 - T K G P S V F P L A P S S K S T S G G T - 140 421 - GCCGCCCTGGGCTGCCTGGTGAAAGACTACTTCCCCGAGCCCGTGACCGTGTCCTGGAAC - 480 141 - A A L G C L V K D Y F P E P V T V S W N - 160 481 - TCTGGCGCCCTGACCAGCGGCGTGCACACCTTTCCAGCCGTGCTGCAGAGCAGCGGCCTG - 540 161 - S G A L T S G V H T F P A V L Q S S G L - 180 541 - TACAGCCTGAGCAGCGTGGTGACAGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATC - 600 181 - Y S L S S V V T V P S S S L G T Q T Y I - 200 601 - TGCAACGTGAACCACAAGCCCAGCAACACCAAGGTGGACAAGAAGGTGGAACCCAAGAGC - 660 201 - C N V N H K P S N T K V D K K V E P K S - 220 661 - TGCGACAAGACCCACACCTGTCCCCCCTGCCCTGCCCCTGAACTGCTGGGCGGACCCAGC - 720 221 - C D K T H T C P P C P A P E L L G G P S - 240 721 - GTGTTCCTGTTCCCGCCGAAACCGAAAGATACCCTGATGATTAGCCGCACCCCGGAAGTG - 780 T P E V - 260 - 840

N W Y V - 280 841 - GATGGCGTGGAAGTGCATAACGCGAAAACCAAACCGCGCGAAGAACAGTATAACAGCACC - 900 281 - D G V E V H N A K T K P R E E Q Y N S T - 300 901 - TATCGCGTGGTGAGCGTGCTGACCGTGCTGCATCAGGATTGGCTGAACGGCAAAGAATAT - 960 301 - Y R V V S V L T V L H Q D W L N G K E Y - 320 961 - AAATGCAAAGTGAGCAACAAAGCGCTGCCGGCGCCGATTGAAAAAACCATTAGCAAAGCG -1020 321 - K C K V S N K A L P A P I E K T I S K A - 340 1021 - AAAGGCCAGCCGCGCGAACCGCAGGTGTATACCCTGCCGCCGAGCCGCGAAGAAATGACC -1080 341 - K G Q P R E P Q V Y T L P P S R E E M T - 360 1081 - AAAAACCAGGTGAGCCTGACCTGCCTGGTGAAAGGCTTTTATCCGAGCGATATTGCGGTG -1140 361 - K N Q V S L T C L V K G F Y P S D I A V - 380 1141 - GAATGGGAAAGCAACGGCCAGCCGGAAAACAACTATAAAACCACCCCGCCGGTGCTGGAT -1200 381 - E W E S N G Q P E N N Y K T T P P V L D - 400 1201 - AGCGATGGCAGCTTTTTTCTGTATAGCAAACTGACCGTGGATAAAAGCCGCTGGCAGCAG -1260 401 - S D G S F F L Y S K L T V D K S R W Q Q - 420 1261 - GGCAACGTGTTTAGCTGCAGCGTGATGCATGAAGCGCTGCATAACCATTATACCCAGAAA -1320 421 - G N V F S C S V M H E A L H N H Y T Q K - 440 1321 - AGCCTGAGCCTGAGCCCGGGCAAATGA - 1347 441 - S L S L S P G K * - 448 Table VI(E). The cDNA sequence (SEQ ID NO: 12) and amino acid sequence (SEQ ID NO: 13) of CL.B heavy chain. The nucleotide sequence encoding the variable region is underlined. 1 - GAGGTTCAGTTAGTCGAGAGCGGGGGGGGTTTAGTTAAGCCAGGTGGCAGTTTAAGACTG - 60 1 - E V Q L V E S G G G L V K P G G S L R L - 20 61 - TCTTGTGCCGCTTCCGGTTTTACCTTTTCTTCTGCTTGGATGTCTTGGGTGAGACAGGCA - 120 21 - S C A A S G F T F S S A W M S W V R Q A - 40 121 - CCTGGTAAAGGCCTGGAATGGGTTGGAAGGATAAAATCTGAAACCTACGGAGGGACTACA - 180 S E T Y G G T T - 60 - 240

S R D D S K N T - 80 241 - TTGTACTTACAGATGAACTCTTTGAAAACCGAGGACACCGCAGTGTATTACTGTGCTAGA - 300 81 - L Y L Q M N S L K T E D T A V Y Y C A R - 100 301 - GGTGGTGCTGATCATTTTGATCTGTACCTGTACTACGGTGCTATGGATGTTTGGGGACAA - 360 101 - G G A D H F D L Y L Y Y G A M D V W G Q - 120 361 - GGAACTTTGGTCACAGTGTCATCTGCCAGCACTAAAGGGCCCTCTGTGTTCCCTCTGGCC - 420 121 - G T L V T V S S A S T K G P S V F P L A - 140 421 - CCCAGCAGCAAGAGCACATCTGGCGGAACAGCCGCCCTGGGCTGCCTGGTGAAAGACTAC - 480 141 - P S S K S T S G G T A A L G C L V K D Y - 160 481 - TTCCCCGAGCCCGTGACCGTGTCCTGGAACTCTGGCGCCCTGACCAGCGGCGTGCACACC - 540 161 - F P E P V T V S W N S G A L T S G V H T - 180 541 - TTTCCAGCCGTGCTGCAGAGCAGCGGCCTGTACAGCCTGAGCAGCGTGGTGACAGTGCCC - 600 181 - F P A V L Q S S G L Y S L S S V V T V P - 200 601 - AGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGAACCACAAGCCCAGCAACACC - 660 201 - S S S L G T Q T Y I C N V N H K P S N T - 220 661 - AAGGTGGACAAGAAGGTGGAACCCAAGAGCTGCGACAAGACCCACACCTGTCCCCCCTGC - 720 221 - K V D K K V E P K S C D K T H T C P P C - 240 721 - CCTGCCCCTGAACTGCTGGGCGGACCCAGCGTGTTCCTGTTCCCGCCGAAACCGAAAGAT - 780 241 - P A P E L L G G P S V F L F P P K P K D - 260 781 - ACCCTGATGATTAGCCGCACCCCGGAAGTGACCTGCGTGGTGGTGGATGTGAGCCATGAA - 840 261 - T L M I S R T P E V T C V V V D V S H E - 280 841 - GATCCGGAAGTGAAATTTAACTGGTATGTGGATGGCGTGGAAGTGCATAACGCGAAAACC - 900 281 - D P E V K F N W Y V D G V E V H N A K T - 300 901 - AAACCGCGCGAAGAACAGTATAACAGCACCTATCGCGTGGTGAGCGTGCTGACCGTGCTG - 960 301 - K P R E E Q Y N S T Y R V V S V L T V L - 320 961 - CATCAGGATTGGCTGAACGGCAAAGAATATAAATGCAAAGTGAGCAACAAAGCGCTGCCG -1020 321 - H Q D W L N G K E Y K C K V S N K A L P - 340 1021 - GCGCCGATTGAAAAAACCATTAGCAAAGCGAAAGGCCAGCCGCGCGAACCGCAGGTGTAT -1080 341 - A P I E K T I S K A K G Q P R E P Q V Y - 360 1081 - ACCCTGCCGCCGAGCCGCGAAGAAATGACCAAAAACCAGGTGAGCCTGACCTGCCTGGTG -1140 361 - T L P P S R E E M T K N Q V S L T C L V - 380 1141 - AAAGGCTTTTATCCGAGCGATATTGCGGTGGAATGGGAAAGCAACGGCCAGCCGGAAAAC -1200 Q P E N - 400 -1260

L Y S K - 420 1261 - CTGACCGTGGATAAAAGCCGCTGGCAGCAGGGCAACGTGTTTAGCTGCAGCGTGATGCAT -1320 421 - L T V D K S R W Q Q G N V F S C S V M H - 440 1321 - GAAGCGCTGCATAACCATTATACCCAGAAAAGCCTGAGCCTGAGCCCGGGCAAATGA - 1377 441 - E A L H N H Y T Q K S L S L S P G K * - 458 Table VI(F). The cDNA (SEQ ID NO: 14) and amino acid sequence (SEQ ID NO: 15) of CL.D heavy chain. The nucleotide sequence encoding the variable region is underlined. 1 - GAGGTTCAGTTGTTAGAGAGCGGGGGGGGTCTGGTTCAGCCTGGTGGCAGCTTAAGACTG - 60 1 - E V Q L L E S G G G L V Q P G G S L R L - 20 61 - AGTTGTGCCGCTTCTGGTTTTACTTTCTCTAATTATGCAATGTCCTGGGTGAGGCAAGCC - 120

241 - TTACAGATGAACTCTTTGAGAGCTGAGGACACCGCAGTGTATTACTGTGCTAGAGGTTTT - 300 81 - L Q M N S L R A E D T A V Y Y C A R G F - 100 301 - TCTAGATTTGATCATTGGGGACAAGGAACTTTGGTCACAGTGTCATCTGCCAGCACTAAA - 360 101 - S R F D H W G Q G T L V T V S S A S T K - 120 361 - GGGCCCTCTGTGTTCCCTCTGGCCCCCAGCAGCAAGAGCACATCTGGCGGAACAGCCGCC - 420 121 - G P S V F P L A P S S K S T S G G T A A - 140 421 - CTGGGCTGCCTGGTGAAAGACTACTTCCCCGAGCCCGTGACCGTGTCCTGGAACTCTGGC - 480 141 - L G C L V K D Y F P E P V T V S W N S G - 160 481 - GCCCTGACCAGCGGCGTGCACACCTTTCCAGCCGTGCTGCAGAGCAGCGGCCTGTACAGC - 540 161 - A L T S G V H T F P A V L Q S S G L Y S - 180 541 - CTGAGCAGCGTGGTGACAGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAAC - 600 181 - L S S V V T V P S S S L G T Q T Y I C N - 200 601 - GTGAACCACAAGCCCAGCAACACCAAGGTGGACAAGAAGGTGGAACCCAAGAGCTGCGAC - 660 201 - V N H K P S N T K V D K K V E P K S C D - 220 661 - AAGACCCACACCTGTCCCCCCTGCCCTGCCCCTGAACTGCTGGGCGGACCCAGCGTGTTC - 720 221 - K T H T C P P C P A P E L L G G P S V F - 240 721 - CTGTTCCCGCCGAAACCGAAAGATACCCTGATGATTAGCCGCACCCCGGAAGTGACCTGC - 780 E V T C - 260 - 840

Y V D G - 280 841 - GTGGAAGTGCATAACGCGAAAACCAAACCGCGCGAAGAACAGTATAACAGCACCTATCGC - 900 281 - V E V H N A K T K P R E E Q Y N S T Y R - 300 901 - GTGGTGAGCGTGCTGACCGTGCTGCATCAGGATTGGCTGAACGGCAAAGAATATAAATGC - 960 301 - V V S V L T V L H Q D W L N G K E Y K C - 320 961 - AAAGTGAGCAACAAAGCGCTGCCGGCGCCGATTGAAAAAACCATTAGCAAAGCGAAAGGC -1020 321 - K V S N K A L P A P I E K T I S K A K G - 340 1021 - CAGCCGCGCGAACCGCAGGTGTATACCCTGCCGCCGAGCCGCGAAGAAATGACCAAAAAC -1080 341 - Q P R E P Q V Y T L P P S R E E M T K N - 360 1081 - CAGGTGAGCCTGACCTGCCTGGTGAAAGGCTTTTATCCGAGCGATATTGCGGTGGAATGG -1140 361 - Q V S L T C L V K G F Y P S D I A V E W - 380 1141 - GAAAGCAACGGCCAGCCGGAAAACAACTATAAAACCACCCCGCCGGTGCTGGATAGCGAT -1200 381 - E S N G Q P E N N Y K T T P P V L D S D - 400 1201 - GGCAGCTTTTTTCTGTATAGCAAACTGACCGTGGATAAAAGCCGCTGGCAGCAGGGCAAC -1260 401 - G S F F L Y S K L T V D K S R W Q Q G N - 420 1261 - GTGTTTAGCTGCAGCGTGATGCATGAAGCGCTGCATAACCATTATACCCAGAAAAGCCTG -1320 421 - V F S C S V M H E A L H N H Y T Q K S L - 440 1321 - AGCCTGAGCCCGGGCAAATGA - 1341 441 - S L S P G K * - 446 Table(s) VI(G) thru VI(L). Sequences of Antibody Light Chains. Table VI(G). The cDNA sequence (SEQ ID NO: 16) and amino acid sequence (SEQ ID NO: 17) of CL.Z light chain. The nucleotide sequence encoding the variable region is underlined. 1 - GACATACAAATGACCCAGTCTCCTTCTTCTCTGAGCGCATCTGTCGGCGATAGAGTGACT - 60 1 - D I Q M T Q S P S S L S A S V G D R V T - 20 61 - ATTACATGTAGGGCCAGCCAGTCTATCTCTACCTATCTGAATTGGTATCAGCAAAAACCC - 120 21 - I T C R A S Q S I S T Y L N W Y Q Q K P - 40 121 - GGCAAGGCTCCAAAACTGTTGATCTATGCTGCTTCAAGCCTGCAATCCGGAGTTCCCTCA - 180 41 - G K A P K L L I Y A A S S L Q S G V P S - 60 181 - AGATTTTCTGGTTCCGGCTCAGGAACTGATTTCACCCTGACTATAAGTTCTTTGCAGCCT - 240 61 - R F S G S G S G T D F T L T I S S L Q P - 80 241 - GAAGACTTTGCAACATATTACTGTCAGCAAGGTTACTCTACCCCACTGACATTCGGGCAA - 300 F G Q - 100 - 360

F P P - 120 361 - AGTGACGAACAGCTGAAAAGCGGGACTGCCTCCGTGGTCTGTCTGCTGAACAATTTCTAC - 420 121 - S D E Q L K S G T A S V V C L L N N F Y - 140 421 - CCCCGGGAAGCCAAGGTGCAGTGGAAAGTCGATAACGCTCTGCAGTCAGGCAATAGCCAG - 480 141 - P R E A K V Q W K V D N A L Q S G N S Q - 160 481 - GAGTCCGTGACCGAACAGGACTCTAAGGATAGTACATATTCACTGAGTTCAACTCTGACC - 540 161 - E S V T E Q D S K D S T Y S L S S T L T - 180 541 - CTGTCCAAAGCAGACTACGAGAAGCATAAAGTGTATGCCTGTGAAGTCACCCACCAGGGG - 600 181 - L S K A D Y E K H K V Y A C E V T H Q G - 200 601 - CTGTCCTCACCAGTCACTAAGTCCTTCAATAGGGGCGAATGCTGA - 645 201 - L S S P V T K S F N R G E C * - 214 Table VI(H). The cDNA sequence (SEQ ID NO: 18) and amino acid sequence (SEQ ID NO: 19) of CL.X light chain. The nucleotide sequence encoding the variable region is underlined. 1 - GAAATCGTCTTGACCCAGTCCCCAGGTACTCTGTCTTTAAGTCCCGGGGAAAGAGCTACT - 60 1 - E I V L T Q S P G T L S L S P G E R A T - 20 61 - CTGTCCTGTAGGGCAAGTCAGTCTGTTTCTTCTAATTATCTGGCCTGGTATCAGCAAAAA - 120 21 - L S C R A S Q S V S S N Y L A W Y Q Q K - 40 121 - CCCGGTCAAGCTCCAAGACTGTTGATCTATGGTGCAAGCAGTAGAGCCACCGGAATCCCT - 180 41 - P G Q A P R L L I Y G A S S R A T G I P - 60 181 - GATAGGTTTTCCGGTTCAGGCAGCGGAACTGACTTCACTCTGACAATCTCAAGATTGGAA - 240 61 - D R F S G S G S G T D F T L T I S R L E - 80 241 - CCTGAGGATTTTGCCGTGTATTACTGTCAGCAATACGGTACCTCTCTGCTGACATTCGGG - 300 81 - P E D F A V Y Y C Q Q Y G T S L L T F G - 100 301 - CAAGGTACCAAGGTCGAGATCAAACGCACAGTGGCCGCTCCATCTGTCTTCATTTTTCCA - 360 101 - Q G T K V E I K R T V A A P S V F I F P - 120 361 - CCCAGTGACGAACAGCTGAAAAGCGGGACTGCCTCCGTGGTCTGTCTGCTGAACAATTTC - 420 121 - P S D E Q L K S G T A S V V C L L N N F - 140 421 - TACCCCCGGGAAGCCAAGGTGCAGTGGAAAGTCGATAACGCTCTGCAGTCAGGCAATAGC - 480 141 - Y P R E A K V Q W K V D N A L Q S G N S - 160 481 - CAGGAGTCCGTGACCGAACAGGACTCTAAGGATAGTACATATTCACTGAGTTCAACTCTG - 540 161 - Q E S V T E Q D S K D S T Y S L S S T L - 180 541 - ACCCTGTCCAAAGCAGACTACGAGAAGCATAAAGTGTATGCCTGTGAAGTCACCCACCAG - 600 181 - T L S K A D Y E K H K V Y A C E V T H Q - 200 601 - GGGCTGTCCTCACCAGTCACTAAGTCCTTCAATAGGGGCGAATGCTGA - 648 201 - G L S S P V T K S F N R G E C * - 215 Table VI(I). The cDNA sequence (SEQ ID NO: 20) and amino acid sequence (SEQ ID NO: 21) of CL.N light chain. The nucleotide sequence encoding the variable region is underlined. 1 - CAGTCCGTGTTGACCCAGCCTCCATCAGTCTCAGGAGCCCCAGGCCAGAGAGTGACCATT - 60 1 - Q S V L T Q P P S V S G A P G Q R V T I - 20 61 - TCTTGTACTGGATCTTCCTCAAATATCGGGGCCGGTTACGATGTTCATTGGTATCAGCAA - 120 21 - S C T G S S S N I G A G Y D V H W Y Q Q - 40 121 - CTGCCCGGTACAGCTCCAAAACTGTTGATCTATGATAATAGAAACAGACCTAGCGGTGTG - 180 41 - L P G T A P K L L I Y D N R N R P S G V - 60 181 - CCCGACAGGTTCTCCGGCTCAAAGAGCGGAACAAGTGCTTCTTTAGCAATTACCGGCCTG - 240 61 - P D R F S G S K S G T S A S L A I T G L - 80 241 - CAGGCTGAAGATGAGGCAGACTATTACTGTCAATCCTACGATACCTCTCTGTCTGCTTGG - 300 81 - Q A E D E A D Y Y C Q S Y D T S L S A W - 100 301 - GTTTTTGGTGGCGGTACCAAATTGACTGTCTTAGGCCAGCCAAAGGCCGCTCCTTCCGTC - 360 101 - V F G G G T K L T V L G Q P K A A P S V - 120 361 - ACCTTGTTCCCACCTTCTTCCGAAGAGTTACAAGCTAACAAAGCAACTCTGGTTTGCTTG - 420 121 - T L F P P S S E E L Q A N K A T L V C L - 140 421 - ATATCTGATTTTTATCCTGGGGCAGTGACAGTTGCCTGGAAAGCTGACTCAAGCCCCGTC - 480 141 - I S D F Y P G A V T V A W K A D S S P V - 160 481 - AAGGCCGGCGTGGAAACTACAACCCCAAGCAAACAGAGTAATAACAAGTATGCAGCCAGT - 540 161 - K A G V E T T T P S K Q S N N K Y A A S - 180 541 - TCTTACTTATCTCTGACTCCCGAGCAATGGAAGTCCCATAGATCCTACTCATGTCAAGTC - 600 181 - S Y L S L T P E Q W K S H R S Y S C Q V - 200 601 - ACCCACGAGGGCTCTACAGTCGAAAAGACCGTCGCACCAACCGAGTGTTCCTAA - 654 201 - T H E G S T V E K T V A P T E C S * - 217 Table VI(J). The cDNA sequence (SEQ ID NO: 22) and amino acid sequence (SEQ ID NO: 23) of CL.I light chain. The nucleotide sequence encoding the variable region is underlined. 1 - GACATACAAATGACCCAGTCTCCTTCTTCTCTGAGCGCATCTGTCGGCGATAGAGTGACT - 60 S L S A S V G D R V T - 20 - 120

S R Y L N W Y Q Q K P - 40 121 - GGCAAGGCTCCAAAACTGTTGATCAATGCTGCTTCAAGCCTGCAATCCGGAGTTCCCTCA - 180 41 - G K A P K L L I N A A S S L Q S G V P S - 60 181 - AGATTTTCTGGTTCCGGCTCAGGAACTGATTTCACCCTGACTATAAGTTCTTTGCAGCCT - 240 61 - R F S G S G S G T D F T L T I S S L Q P - 80 241 - GAAGACTTTGCAACATATTACTGTCAGCAAGGTTACTCTACCCCACCAACATTCGGGCAA - 300 81 - E D F A T Y Y C Q Q G Y S T P P T F G Q - 100 301 - GGTACCAAGGTCGAGATCAAACGCACAGTGGCCGCTCCATCTGTCTTCATTTTTCCACCC - 360 101 - G T K V E I K R T V A A P S V F I F P P - 120 361 - AGTGACGAACAGCTGAAAAGCGGGACTGCCTCCGTGGTCTGTCTGCTGAACAATTTCTAC - 420 121 - S D E Q L K S G T A S V V C L L N N F Y - 140 421 - CCCCGGGAAGCCAAGGTGCAGTGGAAAGTCGATAACGCTCTGCAGTCAGGCAATAGCCAG - 480 141 - P R E A K V Q W K V D N A L Q S G N S Q - 160 481 - GAGTCCGTGACCGAACAGGACTCTAAGGATAGTACATATTCACTGAGTTCAACTCTGACC - 540 161 - E S V T E Q D S K D S T Y S L S S T L T - 180 541 - CTGTCCAAAGCAGACTACGAGAAGCATAAAGTGTATGCCTGTGAAGTCACCCACCAGGGG - 600 181 - L S K A D Y E K H K V Y A C E V T H Q G - 200 601 - CTGTCCTCACCAGTCACTAAGTCCTTCAATAGGGGCGAATGCTGA - 645 201 - L S S P V T K S F N R G E C * - 214 Table VI(K). The cDNA sequence (SEQ ID NO: 24) and amino acid sequence (SEQ ID NO: 25) of CL.B light chain. The nucleotide sequence encoding the variable region is underlined. 1 - GACATACAAATGACCCAGTCTCCTTCTTCTCTGAGCGCATCTGTCGGCGATAGAGTGACT - 60 S L S A S V G D R V T - 20 - 120

Y T Y L N W Y Q Q K P - 40 121 - GGCAAGGCTCCAAAACTGTTGATCTATGCTGCTTCAAGCCTGCAATCCGGAGTTCCCTCA - 180 41 - G K A P K L L I Y A A S S L Q S G V P S - 60 181 - AGATTTTCTGGTTCCGGCTCAGGAACTGATTTCACCCTGACTATAAGTTCTTTGCAGCCT - 240 61 - R F S G S G S G T D F T L T I S S L Q P - 80 241 - GAAGACTTTGCAACATATTACTGTCAGCAAGGTTACTCTTACCCACCAACATTCGGGCAA - 300 81 - E D F A T Y Y C Q Q G Y S Y P P T F G Q - 100 301 - GGTACCAAGGTCGAGATCAAACGCACAGTGGCCGCTCCATCTGTCTTCATTTTTCCACCC - 360 101 - G T K V E I K R T V A A P S V F I F P P - 120 361 - AGTGACGAACAGCTGAAAAGCGGGACTGCCTCCGTGGTCTGTCTGCTGAACAATTTCTAC - 420 121 - S D E Q L K S G T A S V V C L L N N F Y - 140 421 - CCCCGGGAAGCCAAGGTGCAGTGGAAAGTCGATAACGCTCTGCAGTCAGGCAATAGCCAG - 480 141 - P R E A K V Q W K V D N A L Q S G N S Q - 160 481 - GAGTCCGTGACCGAACAGGACTCTAAGGATAGTACATATTCACTGAGTTCAACTCTGACC - 540 161 - E S V T E Q D S K D S T Y S L S S T L T - 180 541 - CTGTCCAAAGCAGACTACGAGAAGCATAAAGTGTATGCCTGTGAAGTCACCCACCAGGGG - 600 181 - L S K A D Y E K H K V Y A C E V T H Q G - 200 601 - CTGTCCTCACCAGTCACTAAGTCCTTCAATAGGGGCGAATGCTGA - 645 201 - L S S P V T K S F N R G E C * - 214 Table VI(L). The cDNA sequence (SEQ ID NO: 26) and amino acid sequence (SEQ ID NO: 27) of CL.D light chain. The nucleotide sequence encoding the variable region is underlined. 1 - GAAATCGTCTTGACCCAGTCCCCAGGTACTCTGTCTTTAAGTCCCGGGGAAAGAGCTACT - 60 1 - E I V L T Q S P G T L S L S P G E R A T - 20 61 - CTGTCCTGTAGGGCAACTCAGTCTGTTTCTGGTTCTTATCTGGCCTGGTATCAGCAAAAA - 120 21 - L S C R A T Q S V S G S Y L A W Y Q Q K - 40 121 - CCCGGTCAAGCTCCAAGACTGTTGATCTATGGTGCAAGCAGTAGAGCCACCGGAATCCCT - 180 41 - P G Q A P R L L I Y G A S S R A T G I P - 60 181 - GATAGGTTTTCCGGTTCAGGCAGCGGAACTGACTTCACTCTGACAATCTCAAGATTGGAA - 240 61 - D R F S G S G S G T D F T L T I S R L E - 80 241 - CCTGAGGATTTTGCCGTGTATTACTGTCAGCAATACGCTTCTTGGCCAGGTACATTCGGG - 300 81 - P E D F A V Y Y C Q Q Y A S W P G T F G - 100 301 - CAAGGTACCAAGGTCGAGATCAAACGCACAGTGGCCGCTCCATCTGTCTTCATTTTTCCA - 360 101 - Q G T K V E I K R T V A A P S V F I F P - 120 361 - CCCAGTGACGAACAGCTGAAAAGCGGGACTGCCTCCGTGGTCTGTCTGCTGAACAATTTC - 420 121 - P S D E Q L K S G T A S V V C L L N N F - 140 421 - TACCCCCGGGAAGCCAAGGTGCAGTGGAAAGTCGATAACGCTCTGCAGTCAGGCAATAGC - 480 141 - Y P R E A K V Q W K V D N A L Q S G N S - 160 481 - CAGGAGTCCGTGACCGAACAGGACTCTAAGGATAGTACATATTCACTGAGTTCAACTCTG - 540 161 - Q E S V T E Q D S K D S T Y S L S S T L - 180 541 - ACCCTGTCCAAAGCAGACTACGAGAAGCATAAAGTGTATGCCTGTGAAGTCACCCACCAG - 600 181 - T L S K A D Y E K H K V Y A C E V T H Q - 200 601 - GGGCTGTCCTCACCAGTCACTAAGTCCTTCAATAGGGGCGAATGCTGA - 648 201 - G L S S P V T K S F N R G E C * - 215 Table(s) VII(A) thru VII(F). Amino Acid Sequences of Antibody Heavy Chains. Table VII(A). Amino acid sequence (SEQ ID NO: 28) of CL.Z heavy chain. The variable region is underlined, and the Kabat CDR regions are boxed. QVQLVESGGGVVQPGRSLRLSCAASGFSFSAYGMHWVRQAPGKGLEWVAVISYDGSYKYYADSVKGR FTISRDNSKNTLYLQMNSLRAEDTAVYYCARGVGAFPWVFFDYWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Table VII(B). Amino acid sequence (SEQ ID NO: 29) of CL.X heavy chain. The variable region is underlined, and the Kabat CDR regions are boxed. QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAFSWVRQAPGQGLEWMGRILPIFGTTNYAQKFQGR VTITADESTSTAYMELSSLRSEDTAVYYCARQAGGVLDVWGQGTLVTVSSASTKGPSVFPLAPSSKST SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Table VII(C). Amino acid sequence (SEQ ID NO: 30) of CL.N heavy chain. The variable region is underlined, and the Kabat CDR regions are boxed. QVQLVESGGGVVQPGRSLRLSCAASGFTFGGYGMHWVRQAPGKGLEWVAVISYSGSNKYYADSVKGR FTISRDNSKNTLYLQMNSLRAEDTAVYYCARGTFVGGAYHYLDPWGQGTLVTVSSASTKGPSVFPLAP SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV SHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Table VII(D). Amino acid sequence (SEQ ID NO: 31) of CL.I heavy chain. The variable region is underlined, and the Kabat CDR regions are boxed. QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMHWVRQAPGKGLEWVAVISFEGSNKYYADSVKGR FTISRDNSKNTLYLQMNSLRAEDTAVYYCARRHYSYGFDVWGQGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Table VII(E). Amino acid sequence (SEQ ID NO: 32) of CL.B heavy chain. The variable region is underlined, and the Kabat CDR regions are boxed. EVQLVESGGGLVKPGGSLRLSCAASGFTFSSAWMSWVRQAPGKGLEWVGRIKSETYGGTTDYAAPVK GRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARGGADHFDLYLYYGAMDVWGQGTLVTVSSASTKGP SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Table VII(F). Amino acid sequence (SEQ ID NO: 33) of CL.D heavy chain. The variable region is underlined, and the Kabat CDR regions are boxed.

GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Table(s) VII(G) thru VII(L). Amino Acid Sequences of Antibody Light Chains. Table VII(G). Amino acid sequence (SEQ ID NO: 34) of CL.Z light chain. The variable region is underlined, and the Kabat CDR regions are boxed. DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGS GTDFTLTISSLQPEDFATYYCQQGYSTPLTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC Table VII(H). Amino acid sequence (SEQ ID NO: 35) of CL.X light chain. The variable region is underlined, and the Kabat CDR regions are boxed. EIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSG SGTDFTLTISRLEPEDFAVYYCQQYGTSLLTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVC LLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS SPVTKSFNRGEC Table VII(I). Amino acid sequence (SEQ ID NO: 36) of CL.N light chain. The variable region is underlined, and the Kabat CDR regions are boxed. QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYDNRNRPSGVPDRFSGS KSGTSASLAITGLQAEDEADYYCQSYDTSLSAWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKA TLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHE GSTVEKTVAPTECS Table VII(J). Amino acid sequence (SEQ ID NO: 37) of CL.I light chain. The variable region is underlined, and the Kabat CDR regions are boxed. DIQMTQSPSSLSASVGDRVTITCRASQSISRYLNWYQQKPGKAPKLLINAASSLQSGVPSRFSGSGS GTDFTLTISSLQPEDFATYYCQQGYSTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC Table VII(K). Amino acid sequence (SEQ ID NO: 38) of CL.B light chain. The variable region is underlined, and the Kabat CDR regions are boxed. DIQMTQSPSSLSASVGDRVTITCRASQSIYTYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGS GTDFTLTISSLQPEDFATYYCQQGYSYPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS PVTKSFNRGEC Table VII(L). Amino acid sequence (SEQ ID NO: 39) of CL.D light chain. The variable region is underlined, and the Kabat CDR regions are boxed. EIVLTQSPGTLSLSPGERATLSCRATQSVSGSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSG SGTDFTLTISRLEPEDFAVYYCQQYASWPGTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVC LLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS SPVTKSFNRGEC Table VIII. Amino Acid Sequences of Antibody Heavy Chain Variable Region(s). CL.Z

CL.D

Table IX. Amino Acid Sequences of Antibody Light Chain Variable Region(s). CL.Z

Table X. Amino Acid Sequences of Antibody CDRs.

Table XI(A) thru XI(F). Alignment of Amino Acid Variable Heavy Chain Regions with Corresponding Germline Sequences. Table XI(A). Alignment of amino acid sequence of CL.Z heavy chain variable region (SEQ ID NO: 88) with corresponding top V (SEQ ID NO: 89), D (SEQ ID NO: 90), and J (SEQ ID NO: 91) germline sequences. The Kabat CDR regions are boxed. CL.Z QVQLVESGGGVVQPGRSLRLSCAASGFSFS WVRQAPGKGLEWVAVISYDGSYKY 59 IGHV3-30*04 QVQLVESGGGVVQPGRSLRLSCAASGFTFS

WVRQAPGKGLEWVAVISYDGSNKY 59 IGHD2-21*01 ----------------------------------------------------------- 0 IGHJ4*01 ----------------------------------------------------------- 0 CL.Z RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGVGAFPWVFFDYWGQGTLVT 118 IGHV3-30*04

RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR--------------------- 98 IGHD2-21*01 -----------------------------------------SILWWLLF----------- 8 IGHJ4*01 ------------------------------------------------YFDYWGQGTLVT 12 CL.Z VSS 121 IGHV3-30*04 --- 98 IGHD2-21*01 --- 8 IGHJ4*01 VSS 15 Table XI(B). Alignment of amino acid sequence of CL.X heavy chain variable region (SEQ ID NO: 92) with corresponding top V (SEQ ID NO: 93), D (SEQ ID NO: 94), and J (SEQ ID NO: 95) germline sequences. The Kabat CDR regions are boxed. CL.X QVQLVQSGAEVKKPGSSVKVSCKASGGTFS WVRQAPGQGLEWMGRILPIFGTTNY 60 IGHV1-69*15 QVQLVQSGAEVKKPGSSVKVSCKASGGTFS

WVRQAPGQGLEWMGRIIPIFGTANY 60 IGHD2-8*02 ------------------------------------------------------------ 0 IGHJ3*01 ------------------------------------------------------------ 0 CL.X 117 IGHV1-69*15 ------------------ 98 IGHD2-8*02

---------------------RILYWWCMLY---------- 10 IGHJ3*01 ------------------------------------------DAFDVWGQGTMVTVSS 16 Table XI(C). Alignment of amino acid sequence of CL.N heavy chain variable region (SEQ ID NO: 96) with corresponding top V (SEQ ID NO: 97), D (SEQ ID NO: 98), and J (SEQ ID NO: 99) germline sequences. The Kabat CDR regions are boxed. CL.N QVQLVESGGGVVQPGRSLRLSCAASGFTFGGYGMHWVRQAPGKGLEWVAVISYSGSNKY 59 IGHV3-30*04 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKY 59 IGHD2-21*01 ------------------------------------------------- -------- 8 IGHJ4*01 ------------------------------------------------------------ 0 CL.N RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGTFVGGAYHYLDPWGQGTLVT 119 IGHV3-30*04

RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR--------------------- 98 IGHD2-21*01 ----------------------------------------SILWWLLF------------- 8 IGHJ4*01 -------------------------------------------------YFDYWGQGTLVT 12 CL.N VSS 122 IGHV3-30*04 --- 98 IGHD2-21*01 --- 8 IGHJ4*01 VSS 15 Table XI(D). Alignment of amino acid sequence of CL.I heavy chain variable region (SEQ ID NO: 100) with corresponding top V (SEQ ID NO: 101), D (SEQ ID NO: 102), and J (SEQ ID NO: 103) germline sequences. The Kabat CDR regions are boxed. CL.I QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYDMHWVRQAPGKGLEWVAVISFEGSNKY 59 IGHV3-30*04 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKY 59 IGHD3-10*01 ------------------------------------------------------------ 9 IGHJ3*01 ------------------------------------------------------------ 0 CL.I RFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRHYSYGFDVWGQGTLVTVSS 118 IGHV3-30*04

RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR-------------------- 98 IGHD3-10*01 ---------------------------------------VLLWFGELL------------ 9 IGHJ3*01 --------------------------------------------DAFDVWGQGTMVTVSS 16 Table XI(E). Alignment of amino acid sequence of CL.B heavy chain variable region (SEQ ID NO: 104) with corresponding top V (SEQ ID NO: 105), D (SEQ ID NO: 106), and J (SEQ ID NO: 107) germline sequences. The Kabat CDR regions are boxed. CL.B EVQLVESGGGLVKPGGSLRLSCAASGFTFSSAWMSWVRQAPGKGLEWVGRIKSETYGGTT 60 IGHV3-15*05 EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTT 60 IGHD2-21*01 ------------------------------------------------------------- 8 IGHJ3*01 ------------------------------------------------------------ 0 CL.B RFTISRDDSKNTLYLQMNSLKTEDTAVYYCARGGADHFDLYLYYGAMDVWG 119 IGHV3-15*05

RFTISRDDSKNTLYLQMNSLKTEDTAVYYCTT------------------- 100 IGHD2-21*01 ----------------------------------------- SILWWLLF---------- 8 IGHJ3*01 -----------------------------------------------------DAFDVWG 7 CL.B QGTLVTVSS 128 IGHV3-15*05 --------- 100 IGHD2-21*01 --------- 8 IGHJ3*01 QGTMVTVSS 16 Table XI(F). Alignment of amino acid sequence of CL.D heavy chain variable region (SEQ ID NO: 108) with corresponding top V (SEQ ID NO: 109), D (SEQ ID NO: 110), and J (SEQ ID NO: 111) germline sequences. The Kabat CDR regions are boxed. CL.D EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGLEWVSTISPGGGNTD 59

IGHD3-16*03 ------------------------------------VLLHLGELSLY----------- 11 IGHJ4*01 -------------------------------------------YFDYWGQGTLVTVSS 15 Table XI(G) thru XI(L). Alignment of Amino Acid Variable Light Chain Regions with Corresponding Germline Sequences Table XI(G). Alignment of amino acid sequence of CL.Z light chain variable region (SEQ ID NO: 112) with corresponding top V (SEQ ID NO: 113) and J (SEQ ID NO: 114) germline sequences. The Kabat CDR regions are boxed.

CL.Z RFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSTPLTFGQGTKVEIK 107 IGKV1-39*01 RFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTP------------ 95 IGKJ1*01 ------------------------------------WTFGQGTKVEIK 12 Table XI(H). Alignment of amino acid sequence of CL.X light chain variable region (SEQ ID NO: 115) with corresponding top V (SEQ ID NO: 116) and J (SEQ ID NO: 117) germline sequences. The Kabat CDR regions are boxed.

CL.X DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGTSLLTFGQGTKVEIK 108 IGKV3-20*01 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSP------------ 96 IGKJ1*01 -------------------------------------WTFGQGTKVEIK 12 Table XI(I). Alignment of amino acid sequence of CL.N light chain variable region (SEQ ID NO: 118) with corresponding top V (SEQ ID NO: 119) and J (SEQ ID NO: 120) germline sequences. The Kabat CDR regions are boxed. CL.N QSVLTQPPSVSGAPGQRVTISC WYQQLPGTAPKLLIY 58 IGLV1-44*01 QSVLTQPPSASGTPGQRVTISC

WYQQLPGTAPKLLIY

57 IGLJ5*01 ------------------------------------------------------------ 0

IGLV1-44*01 GVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNG------------ 98 IGLJ5*01 -------------------------------------------WVFGEGTELTVL 12 Table XI(J). Alignment of amino acid sequence of CL.I light chain variable region (SEQ ID NO: 121) with corresponding top V (SEQ ID NO: 122) and J (SEQ ID NO: 123) germline sequences. The Kabat CDR regions are boxed.

CL.I RFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSTPPTFGQGTKVEIK 107 IGKV1-39*01 RFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTP------------ 95 IGKJ1*01 ------------------------------------WTFGQGTKVEIK 12 Table XI(K). Alignment of amino acid sequence of CL.B light chain variable region (SEQ ID NO: 124) with corresponding top V (SEQ ID NO: 125) and J (SEQ ID NO: 126) germline sequences. The Kabat CDR regions are boxed.

CL.B RFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSYPPTFGQGTKVEIK 107 IGKV1-39*01 RFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTP------------ 95 IGKJ1*01 ------------------------------------WTFGQGTKVEIK 12 Table XI(L). Alignment of amino acid sequence of CL.D light chain variable region (SEQ ID NO: 127) with corresponding top V (SEQ ID NO: 128) and J (SEQ ID NO: 129) germline sequences. The Kabat CDR regions are boxed. CL.D EIVLTQSPGTLSLSPGERATLSC WYQQKPGQAPRLLIY GIP 60 IGKV3-20*01 EIVLTQSPGTLSLSPGERATLSC

WYQQKPGQAPRLLIY

GIP 60 IGKJ1*01 ------------------------------------------------------------ 0 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYASWPGTFGQGTKVEIK 108 IGKV3-20*01 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSP------------ 96 IGKJ1*01 -------------------------------------WTFGQGTKVEIK 12 Table XII. Summarizes the ratio of mean fluorescence intensity (MFIR) values of the binding of the various Nectin-4 antibodies to the human breast cancer cell line T-47D.

Table XIII. Summarizes the binding parameters Bmax, K_D , and Fit curve R2 of the various Nectin-4 antibodies and derived ADCs to the human lung cancer cell line NCI-H292.

Table XIV. Summarizes the in vitro cytotoxicity potencies (IC₅₀) in the Nectin4-positive cell lines, NCI- H322 and PC3-Nectin4, as well as the Nectin4-negative cell line PC3.

Table XV. Summarizes the in vitro cytotoxicity potencies (IC₅₀) of Nectin-4 ADCs containing nine (9 different linker-payloads in the Nectin-4 positive cell line PC3-Nectin4.

Table XVI. Summarizes the toxicokinetic parameters of ADC and total IgG antibody after intravenous administration of Ab5-ADC2 in cynomolgus monkeys at 6, 12 or 18 mg/kg.

Claims

CLAIMS: 1) An antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 52, SEQ ID NO: 53, and SEQ ID NO: 54. 2) An antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57. 3) An antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 58, SEQ ID NO: 59, and SEQ ID NO: 60. 4) An antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 61, SEQ ID NO: 62, and SEQ ID NO: 63. 5) An antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 64, SEQ ID NO: 65, and SEQ ID NO: 66. 6) An antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) having the sequences set forth in SEQ ID NO: 67, SEQ ID NO: 68, and SEQ ID NO: 69. 7) The antibody or antigen binding fragment thereof of any of claims 1-6, wherein the antibody or antigen binding fragment thereof is conjugated to a drug via a linker. 8) The antibody or antigen binding fragment thereof of claim 7, wherein the drug is an auristatin analog. 9) An antibody drug conjugate (ADC) comprising a NECTIN-4 antibody or antigen binding fragment thereof conjugated to a Drug-Linker (DL) payload, wherein the antibody or antigen binding fragment thereof comprises the antibody of any of claims 1-6. 10) The ADC of claim 9, wherein the DL payload comprises the following chemical structure: H O H H O H O N N N N N N N N N .

O H H O H O N N N N N N N .

H O O H H O N N N N N .

H O H O H O N N N N N .

14) The ADC of claim 9, wherein the DL payload comprises the following chemical structure: H O H O H O .

15) The ADC of claim 9, wherein the DL payload comprises the following chemical structure: N O O Br .

16) The ADC of claim 9, wherein the DL payload comprises the following chemical structure: N H O H O H Br N N N N N N N N N .

N H O O Br H H N N N N N N N N .

N H O H O H Br N N N N N N .

N H O H O H Br N N N N N N .

N H O H H O H Br .

21) The ADC of claim 9, wherein the DL payload comprises the following chemical structure: O OH Br .

22) The ADC of claim 9, wherein the DL payload comprises the following chemical structure: O OH H O H O H O Br .

O OH O O O Br .

O OH O Br .

O OH Br .

any a pharmaceutically acceptable excipient. 27) A kit comprising the ADC of any of claims 9-25. 28) A kit comprising the pharmaceutical composition of claim 26. 29) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of an ADC of any of claims 9-25. 30) A method of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 26. 31) The method of claim 29, wherein the subject is a human. 32) The method of claim 30, wherein the subject is a human. 33) The method of claim 29, wherein the cancer is set forth in Table I. 34) The method of claim 30, wherein the cancer is set forth in Table I. 35) The method of claim 29, wherein the method further comprises administering radiation or a chemotherapeutic agent or CAR-T therapy, or NK cell therapy. 36) The method of claim 30, wherein the method further comprises administering radiation or a chemotherapeutic agent or CAR-T therapy, or NK cell therapy.