CN115433278A - Binding to CS1 protein rabbit recombinant monoclonal antibody and its application - Google Patents

Abstract

The invention relates to a CS1 protein-bound rabbit recombinant monoclonal antibody and application thereof, wherein the obtained antibody has good specificity, and most importantly, the antibody has high affinity and good specificity, and can make up for the diagnosis and treatment-related application of the CS1 protein-bound rabbit recombinant monoclonal antibody in the market.

Description

Translated fromChinese

结合CS1蛋白兔重组单克隆抗体及应用Binding to CS1 protein rabbit recombinant monoclonal antibody and its application

技术领域technical field

本发明属于生物技术领域，特别是涉及能特异结合CS1蛋白的兔重组单克隆抗体及应用。The invention belongs to the field of biotechnology, in particular to a rabbit recombinant monoclonal antibody capable of specifically binding CS1 protein and its application.

背景技术Background technique

表面抗原CD319，是靶向信号淋巴细胞激活分子家族成员7（signalinglymphocytic activation molecule F7 ，SLAMF7），又称为CS1，它是一种表达于骨髓瘤细胞表面的糖蛋白，同时也表达于自然杀伤细胞和浆细胞表面，在造血谱系分化细胞的特定免疫细胞亚群种也有低量表达。 CS1是多发性骨髓瘤中正常浆细胞和恶性浆细胞的强标记物。目前，CS1是免疫治疗多发性骨髓瘤的热门靶点之一。另外，有研究发现CS1是否存在于病人的癌症中可能有助于一开始确定CD47抑制剂是否是一种好的治疗选择。因此，开发CS1的单克隆抗体对于多发性骨髓瘤的诊断和治疗具有重要的价值。The surface antigen CD319 is a member of the signaling lymphocyte activation molecule family 7 (signalinglymphocytic activation molecule F7, SLAMF7), also known as CS1, which is a glycoprotein expressed on the surface of myeloma cells and also expressed on natural killer cells It is also expressed at low levels on the surface of plasma cells and specific immune cell subpopulations of differentiated cells of the hematopoietic lineage. CS1 is a strong marker of normal and malignant plasma cells in multiple myeloma. Currently, CS1 is one of the popular targets for immunotherapy for multiple myeloma. Additionally, studies finding whether CS1 is present in patients' cancers may help determine whether CD47 inhibitors are a good treatment option in the first place. Therefore, the development of CS1 monoclonal antibody is of great value for the diagnosis and treatment of multiple myeloma.

目前现有技术中，已经开发了靶向CS1的抗体。例如中国专利申请CN2004800164542公开了抗CS1抗体的治疗用途，CN2009801458197公开了抗CS1抗体用于治疗罕见淋巴瘤的用途。虽然上述抗体也具有一定的应用前景，但是仍然需要开发亲和力更强、表位更多的单克隆抗体。In the current state of the art, antibodies targeting CS1 have been developed. For example, Chinese patent application CN2004800164542 discloses the therapeutic use of anti-CS1 antibody, and CN2009801458197 discloses the use of anti-CS1 antibody for treating rare lymphoma. Although the above-mentioned antibodies also have certain application prospects, it is still necessary to develop monoclonal antibodies with stronger affinity and more epitopes.

发明内容Contents of the invention

本发明目的在于提供能特异结合CS1蛋白的兔重组单克隆抗体，选自以下兔重组单克隆抗体的一种或多种：The purpose of the present invention is to provide a rabbit recombinant monoclonal antibody that can specifically bind to the CS1 protein, which is selected from one or more of the following rabbit recombinant monoclonal antibodies:

命名为1D12的兔重组单克隆抗体：其重链互补决定区CDR1、CDR2、CDR3的氨基酸序列分别为SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3所示的氨基酸序列；且轻链互补决定区CDR1、CDR2、CDR3的氨基酸序列分别为SEQ ID NO:4，SEQ ID NO:5、SEQ ID NO:6所示的氨基酸序列；The rabbit recombinant monoclonal antibody named 1D12: the amino acid sequences of its heavy chain complementarity determining regions CDR1, CDR2, and CDR3 are the amino acid sequences shown in SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; and The amino acid sequences of the complementarity determining regions CDR1, CDR2, and CDR3 of the light chain are respectively the amino acid sequences shown in SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6;

命名为1H2的兔重组单克隆抗体：其重链互补决定区CDR1、CDR2、CDR3的氨基酸序列分别为SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12所示的氨基酸序列，且轻链互补决定区CDR1、CDR2、CDR3的氨基酸序列分别为SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15所示的氨基酸序列；The rabbit recombinant monoclonal antibody named 1H2: the amino acid sequences of its heavy chain complementarity determining regions CDR1, CDR2, and CDR3 are respectively the amino acid sequences shown in SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, and The amino acid sequences of the complementarity determining regions CDR1, CDR2, and CDR3 of the light chain are respectively the amino acid sequences shown in SEQ ID NO:13, SEQ ID NO:14, and SEQ ID NO:15;

命名为2B3的兔重组单克隆抗体，其重链互补决定区CDR1、CDR2、CDR3的氨基酸序列分别为SEQ IDNO:19、SEQ ID NO:20、SEQ ID NO:21所示的氨基酸序列，且轻链互补决定区CDR1、CDR2、CDR3的氨基酸序列分别为SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24所示的氨基酸序列；The rabbit recombinant monoclonal antibody named 2B3, the amino acid sequences of its heavy chain complementary determining regions CDR1, CDR2, and CDR3 are respectively the amino acid sequences shown in SEQ ID NO: 19, SEQ ID NO: 20, and SEQ ID NO: 21, and the light The amino acid sequences of the CDR1, CDR2, and CDR3 strand complementarity determining regions are respectively the amino acid sequences shown in SEQ ID NO:22, SEQ ID NO:23, and SEQ ID NO:24;

在上述技术方案的基础上，命名为1D12的兔重组单克隆抗体，其重链可变区序列为SEQ ID NO:7所示的氨基酸序列，且轻链可变区序列为SEQ ID NO:8所示的氨基酸序列；On the basis of the above-mentioned technical scheme, the rabbit recombinant monoclonal antibody named 1D12, its heavy chain variable region sequence is the amino acid sequence shown in SEQ ID NO: 7, and the light chain variable region sequence is SEQ ID NO: 8 the amino acid sequence shown;

命名为1H2的兔重组单克隆抗体，其重链可变区序列为SEQ ID NO:16所示的氨基酸序列，且轻链可变区序列为SEQ ID NO:17所示的氨基酸序列；The rabbit recombinant monoclonal antibody named 1H2, its heavy chain variable region sequence is the amino acid sequence shown in SEQ ID NO: 16, and the light chain variable region sequence is the amino acid sequence shown in SEQ ID NO: 17;

命名为2B3的兔重组单克隆抗体，其重链可变区序列为SEQ ID NO:25所示的氨基酸序列，且轻链可变区序列为SEQ ID NO:26所示的氨基酸序列；The rabbit recombinant monoclonal antibody named 2B3, its heavy chain variable region sequence is the amino acid sequence shown in SEQ ID NO:25, and the light chain variable region sequence is the amino acid sequence shown in SEQ ID NO:26;

在上述技术方案的基础上，命名为1D12的兔重组单克隆抗体，其SCFV序列为SEQID NO:9所示的氨基酸序列；On the basis of the above-mentioned technical scheme, the rabbit recombinant monoclonal antibody named 1D12, its SCFV sequence is the amino acid sequence shown in SEQID NO:9;

命名为1H2的兔重组单克隆抗体，其SCFV序列为SEQ ID NO:18所示的氨基酸序列；The rabbit recombinant monoclonal antibody named 1H2, its SCFV sequence is the amino acid sequence shown in SEQ ID NO: 18;

命名为2B3的兔重组单克隆抗体，其SCFV序列为SEQ ID NO:27所示的氨基酸序列；The rabbit recombinant monoclonal antibody named 2B3, its SCFV sequence is the amino acid sequence shown in SEQ ID NO:27;

在上述技术方案的基础上，兔重组单克隆抗体的轻链恒定区为κ链，重链恒定区为IgG型。On the basis of the above technical scheme, the light chain constant region of the rabbit recombinant monoclonal antibody is a κ chain, and the heavy chain constant region is an IgG type.

本发明还提供一种核酸分子，其包含能够编码结合CS1蛋白的兔重组单克隆抗体的重链互补决定区或轻链互补决定区的核酸序列。The present invention also provides a nucleic acid molecule, which comprises a nucleic acid sequence capable of encoding the heavy chain complementarity determining region or the light chain complementarity determining region of the rabbit recombinant monoclonal antibody binding to the CS1 protein.

本发明还提供一种载体，其含有上述核酸分子。The present invention also provides a vector containing the above-mentioned nucleic acid molecule.

本发明还提供一种宿主细胞，该宿主细胞含有上述结合CS1蛋白的兔重组单克隆抗体、上述核酸分子或上述载体。The present invention also provides a host cell, which contains the above-mentioned rabbit recombinant monoclonal antibody binding to CS1 protein, the above-mentioned nucleic acid molecule or the above-mentioned carrier.

本发明还提供一种偶联物，含有上述抗体。The present invention also provides a conjugate comprising the above antibody.

本发明还提供一种药物组合物，含有主成分和辅成分，其中：主成分上述结合CS1蛋白的兔重组单克隆抗体、上述核酸分子、上述载体、上述宿主细胞、上述偶联物中的一种或多种，辅成分选自药学上可接受的载体或赋形剂，以及任选的其它生物活性物质。The present invention also provides a pharmaceutical composition, which contains a main component and an auxiliary component, wherein: the main component is one of the above-mentioned rabbit recombinant monoclonal antibody binding to CS1 protein, the above-mentioned nucleic acid molecule, the above-mentioned carrier, the above-mentioned host cell, and the above-mentioned conjugate One or more auxiliary components are selected from pharmaceutically acceptable carriers or excipients, and optionally other biologically active substances.

本发明还提供上述结合CS1蛋白的兔重组单克隆抗体、上述核酸分子、上述载体、上述宿主细胞、上述偶联物在制备治疗疾病的药物或检测试剂中的应用。The present invention also provides the application of the above-mentioned rabbit recombinant monoclonal antibody binding to CS1 protein, the above-mentioned nucleic acid molecule, the above-mentioned carrier, the above-mentioned host cell, and the above-mentioned conjugate in the preparation of drugs for treating diseases or detection reagents.

本发明还提供一种试剂盒，该试剂盒包含上述结合CS1蛋白的兔重组单克隆抗体。The present invention also provides a kit, which contains the above-mentioned rabbit recombinant monoclonal antibody binding to CS1 protein.

与现有技术相比，本发明具有以下优点和有益效果：Compared with the prior art, the present invention has the following advantages and beneficial effects:

目前针对CS1单克隆抗体的还没有兔源的，由于兔源抗体的亲和力较鼠源的要高，而且兔子的免疫过程相较于鼠更复杂，可以得到更多表位的抗体，因此，本发明利用B细胞克隆技术提供结合CS1蛋白的兔重组单克隆抗体，重要的是结合CS1蛋白的兔重组单克隆抗体亲和力高，具有良好的特异性，特别是该抗体可以通过流式方式识别天然细胞膜上的CS1蛋白，因此，一方面可以弥补市场上结合CS1蛋白的兔重组单克隆抗体的诊断应用，同时，后期可进行人源化后开发针对CS1靶点的嵌合抗原受体（CAR-T）或双特异性抗体或抗体偶联药物等进行相关疾病的治疗。At present, there is no rabbit-derived monoclonal antibody against CS1. Because the affinity of rabbit-derived antibodies is higher than that of mouse-derived antibodies, and the immunization process of rabbits is more complicated than that of mice, antibodies with more epitopes can be obtained. Therefore, this The invention uses B cell cloning technology to provide a rabbit recombinant monoclonal antibody that binds to CS1 protein. The important thing is that the rabbit recombinant monoclonal antibody that binds to CS1 protein has high affinity and good specificity. In particular, the antibody can recognize natural cell membranes by flow cytometry Therefore, on the one hand, it can make up for the diagnostic application of rabbit recombinant monoclonal antibodies combined with CS1 protein on the market, and at the same time, it can be humanized in the later stage to develop a chimeric antigen receptor (CAR-T ) or bispecific antibodies or antibody-conjugated drugs for the treatment of related diseases.

附图说明Description of drawings

为了更清楚地说明本发明实施例中的技术方案，下面将对实施例描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings that need to be used in the description of the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present invention. For those skilled in the art, other drawings can also be obtained based on these drawings without creative effort.

图1显示了CS1蛋白的SDS电泳图。Figure 1 shows the SDS electropherogram of CS1 protein.

图2 显示了表达纯化的CS1兔重组单克隆抗体的SDS电泳图。Figure 2 shows the SDS electropherogram of the expressed and purified CS1 rabbit recombinant monoclonal antibody.

图3显示了FACs检测CS1兔重组单克隆抗体的结合力。Figure 3 shows the binding ability of CS1 rabbit recombinant monoclonal antibody detected by FACs.

图4-6显示了FACs检测CS1兔重组单克隆抗体的的特异性性。Figures 4-6 show the specificity of FACs for detection of CS1 rabbit recombinant monoclonal antibody.

具体实施方式detailed description

为使本发明实施例的目的、技术方案和优点更加清楚，下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例是本发明的一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动的前提下所获得的所有其他实施例，都属于本发明保护的范围。In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments It is a part of embodiments of the present invention, but not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.

以下对本发明做进一步描述：在本发明中，除非另有说明，否则本文中使用的科学和技术名词具有本领域技术人员所通常理解的含义。并且，本文中所用的蛋白质和核酸化学、分子生物学、细胞和组织培养、微生物学、免疫学相关术语和实验室操作步骤均为相应领域内广泛使用的术语和常规步骤。同时，为了更好地理解本发明，下面提供相关术语的定义和解释。The present invention is further described as follows: In the present invention, unless otherwise specified, scientific and technical terms used herein have meanings commonly understood by those skilled in the art. Moreover, the terms related to protein and nucleic acid chemistry, molecular biology, cell and tissue culture, microbiology, immunology and laboratory operation steps used herein are all terms and routine procedures widely used in the corresponding fields. Meanwhile, in order to better understand the present invention, definitions and explanations of relevant terms are provided below.

这里提到的术语“抗体”包括完整抗体及其任何抗原结合片段 (即“抗原结合部分”)或单链。“抗体”是指包含通过二硫键互相连接在一起的至少两条重(H)链和两条轻(L)链的糖蛋白，或其抗原结合部分。每条重链由重链可变区和重链恒定区组成。本发明中涉及的蛋白或其片段可以是天然纯化的产物，或是化学合成的产物，或使用重组技术从真核宿主（例如哺乳动物细胞）中产生。本发明所用原料及试剂均可由市场购得。The term "antibody" as used herein includes whole antibodies and any antigen-binding fragment (ie, "antigen-binding portion") or single chains thereof. "Antibody" refers to a glycoprotein comprising at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds, or an antigen-binding portion thereof. Each heavy chain is composed of a heavy chain variable region and a heavy chain constant region. The proteins or fragments thereof involved in the present invention may be natural purified products, chemically synthesized products, or produced from eukaryotic hosts (such as mammalian cells) using recombinant techniques. The raw materials and reagents used in the present invention can be purchased from the market.

下面结合实施例，进一步阐述本发明的技术方案。The technical solutions of the present invention will be further described below in conjunction with the examples.

实施例：Example:

（1）CS1蛋白的制备：本发明构建了CS1 FC融合标签蛋白真核表达质粒，转染293F细胞5天后，收集细胞培养基上清，利用proteinA树脂进行纯化，并对蛋白的浓度进行鉴定，蛋白表达纯化鉴定结果见图1。(1) Preparation of CS1 protein: The present invention constructed a eukaryotic expression plasmid of CS1 FC fusion tag protein. After transfecting 293F cells for 5 days, the supernatant of the cell culture medium was collected, purified by protein A resin, and the concentration of the protein was identified. The results of protein expression, purification and identification are shown in Figure 1.

（2）免疫动物外周血单个核细胞（即PBMC细胞）的获取：选择新西兰大白兔作为免疫动物。第一次免疫时将250μg CS1蛋白与等体积的完全弗氏佐剂进行乳化，对新西兰大白兔皮下背部多点进行注射，21天后进行第二次免疫，将120μg的蛋白与等体积的不完全弗氏佐剂进行乳化，对新西兰大白兔背部皮下注射，21天后进行第三次免疫，将120μg的蛋白与等体积的不完全弗氏佐剂进行乳化，对新西兰大白兔背部皮下注射。第三次免疫后间隔一周，无菌采集外周血。(2) Acquisition of peripheral blood mononuclear cells (ie, PBMC cells) from immunized animals: New Zealand white rabbits were selected as immunized animals. For the first immunization, 250 μg of CS1 protein was emulsified with an equal volume of complete Freund’s adjuvant, and injected into the subcutaneous back of New Zealand white rabbits at multiple points. After 21 days, the second immunization was performed, and 120 μg of protein was mixed with an equal volume of incomplete adjuvant. Freund's adjuvant was emulsified, and New Zealand white rabbits were injected subcutaneously on the back. After 21 days, the third immunization was carried out. 120 μg of protein was emulsified with an equal volume of incomplete Freund's adjuvant, and New Zealand white rabbits were injected subcutaneously on the back. One week after the third immunization, peripheral blood was aseptically collected.

（3）CS1特异性B淋巴细胞的获取：用淋巴细胞分离液将所采集的外周血中的PBMC细胞分离出来；按照免疫磁珠操作说明，将CS1蛋白偶联到磁珠上；将CS1蛋白偶联的磁珠与分离出的PBMC细胞共同室温孵育50min后的混合物放入磁力架中，5min后磁珠全部沉入底部，弃掉上清，加入无菌的PBS洗涤细胞，重复洗细胞3次，最后分离得到的细胞即为CS1特异性的B淋巴细胞。(3) Acquisition of CS1-specific B lymphocytes: Separate the PBMC cells in the collected peripheral blood with lymphocyte separation medium; follow the instructions for the operation of immunomagnetic beads, couple the CS1 protein to the magnetic beads; The coupled magnetic beads and the isolated PBMC cells were incubated at room temperature for 50 minutes, and the mixture was placed in the magnetic stand. After 5 minutes, all the magnetic beads sank to the bottom. Discard the supernatant, add sterile PBS to wash the cells, and wash the cells repeatedly for 3 minutes. Second, the final isolated cells are CS1-specific B lymphocytes.

（4）B淋巴细胞的鉴定：将分离获得的B淋巴细胞进行一定倍数的稀释后置入96孔细胞培养板，加入含10%胎牛血清（FBS）和2μg/ml的人IL2的1640培养基，37℃ 5% CO₂条件下培养6天。收集培养基上清进行抗体的鉴定。(4) Identification of B lymphocytes: Dilute the isolated B lymphocytes to a certain number of times and place them in a 96-well cell culture plate, add 1640 culture medium containing 10% fetal bovine serum (FBS) and 2 μg/ml human IL2 cultured at 37°C in 5% CO₂ for 6 days. The culture supernatant was collected for antibody identification.

间接ELISA鉴定：Indirect ELISA identification:

包被浓度为1μg/ml的CS1蛋白，100μl/孔，4℃孵育16h；次日弃掉包被液后用含1%牛血清白蛋白(BSA)的PBS进行封闭，150μl/孔，37℃孵育1h。弃掉封闭液，加入B细胞上清，50μl/孔，37℃孵育1h。弃掉B细胞上清，用含0.5wt.%的Tween-20的PBS洗板5次，2min/次，最后加入稀释5000倍的羊抗兔IgG-HRP二抗，37℃孵育1h。弃掉二抗，用磷酸盐吐温缓冲液（PBST）洗板5次，2min/次。弃掉洗涤液，拍干，加入底物进行显色。标记为1D12、1H2、2B3的B细胞克隆ELISA鉴定为阳性，检测结果见表1。Coat with CS1 protein at a concentration of 1 μg/ml, 100 μl/well, incubate at 4°C for 16 h; discard the coating solution the next day and block with PBS containing 1% bovine serum albumin (BSA), 150 μl/well, incubate at 37°C 1h. Discard the blocking solution, add B cell supernatant, 50 μl/well, and incubate at 37°C for 1 hour. Discard the B cell supernatant, wash the plate with PBS containing 0.5wt.% Tween-20 5 times, 2min each time, and finally add goat anti-rabbit IgG-HRP secondary antibody diluted 5000 times, and incubate at 37°C for 1h. The secondary antibody was discarded, and the plate was washed 5 times with phosphate buffered saline Tween (PBST), 2 min each time. Discard the wash solution, pat dry, and add substrate for color development. The B cell clones labeled 1D12, 1H2, and 2B3 were identified as positive by ELISA, and the test results are shown in Table 1.

表1. ELISA检测结果Table 1. ELISA test results

克隆号clone numberOD450值OD450 value1D121D122.132.131H21H21.521.522B32B32.032.03

（5）抗体基因的克隆(5) Cloning of antibody genes

对经鉴定为阳性的B细胞进行收集，利用常规的RNA提取方法提取RNA后，反转录为cDNA，利用抗体重链的基因引物即：上游引物5’-CAGTCGCTGGAGGAGTCCGG-3’和下游引物5’-CCATTGGTGAGGGTGCCCGAG-3’，抗体轻链基因的引物即：上游引物5’-GACATTGTGATGACCCAGAC-3’和下游引物5’-CCACCTCGGTCCCTTCGCCG-3’，对抗体重轻链基因进行扩增，其扩增条件为：94℃ 3min进行变性，(95℃ 1min，56℃ 30s，72℃1min)进行30个循环反应，最后72℃延伸10min（PCR扩增结果见图2）。利用DNA胶纯化回收试剂盒将PCR产物进行回收。将兔重组单克隆抗体的重轻链基因克隆至表达载体后进行转化，利用菌落PCR验证单菌落，将阳性菌落进行基因测序，即可获得特异性抗体的基因序列。对特异性抗体的基因序列按照密码子翻译即可得到特异性抗体各区域的氨基酸序列。通过标记为1D12，1H2，2B3的B淋巴细胞最终所获得的特异性抗体的氨基酸序列见表2所示。Collect the identified positive B cells, use the conventional RNA extraction method to extract the RNA, reverse transcribe it into cDNA, and use the gene primers of the heavy chain of the antibody: the upstream primer 5'-CAGTCGCTGGAGGAGTCCGG-3' and the downstream primer 5' -CCATTGGTGAGGGTGCCCGAG-3', the primers of the antibody light chain gene are: the upstream primer 5'-GACATTGTGATGACCCAGAC-3' and the downstream primer 5'-CCACCTCGGTCCCTTCGCCG-3', the antibody heavy and light chain gene is amplified, and the amplification conditions are: 94 Denaturation at ℃ for 3 minutes, 30 cycle reactions (95℃ for 1min, 56℃ for 30s, 72℃ for 1min), and finally extension at 72℃ for 10min (see Figure 2 for PCR amplification results). The PCR product was recovered using a DNA gel purification recovery kit. The heavy and light chain genes of the rabbit recombinant monoclonal antibody are cloned into the expression vector and then transformed, and the single colony is verified by colony PCR, and the gene sequence of the positive colony is sequenced to obtain the gene sequence of the specific antibody. The gene sequence of the specific antibody can be translated according to the codons to obtain the amino acid sequence of each region of the specific antibody. The amino acid sequences of the specific antibodies finally obtained from the B lymphocytes labeled 1D12, 1H2, and 2B3 are shown in Table 2.

表2. 特异性抗体的氨基酸序列Table 2. Amino acid sequences of specific antibodies

SEQ ID NO.SEQ ID NO.命名name形式/来源form/source类型Types of序列sequence111D121D12VH CDR1VHCDR1aaaaGFSLSSYGGFSLSSYG221D121D12VH CDR2VHCDR2aaaaINTDGSTINTDGST331D121D12VH CDR3VHCDR3aaaaARGYPGYITDSYYYFNIARGYPGYITDSYYYFNI441D121D12VL CDR1VLCDR1aaaaQSISSYQSISSY551D121D12VL CDR2VLCDR2aaaaRASRAS661D121D12VL CDR3VL CDR3aaaaQCTYGTFHSSGYGQCTYGTFHSSGYG771D121D12VHVHaaaaQSVEESGGRLVTPGTPLTLTCTVSGFSLSSYGMIWVRQAPGKGLEWIGSINTDGSTYYATWAKGRFTISRTSTTVDLKITSPTTEDTATYFCARGYPGYITDSYYYFNIWGPGTLVTVSQSVEESGGRLVTPGTPLTLTTCTVSGFSLSSYGMIWVRQAPGKGLEWIGSINTDGSTYYATWAKGRFTISRTSTTVDLKITSPTTEDTATYFCARGYPGYITDSYYYFNIWGPGTLVTVS881D121D12VLVLaaaaDVVLTQTPASVEAAVRGTVTIKCQASQSISSYLSWYQQKPGQPPKLLIYRASTLESGVPSRFKGSGSGTEFTLTITDLECADAATYYCQCTYGTFHSSGYGFGGGTGVVVKDVVLTQTPASVEAAVRGTVTIKCQASQSISSYLSWYQQKPGQPPKLLIYRASTLESGVPSRFKGSGSGTEFTLTITDLECADAATYYCQCTYGTFHSSGYGFGGGTGVVVK991D121D12scfvscfvaaaaQSVEESGGRLVTPGTPLTLTCTVSGFSLSSYGMIWVRQAPGKGLEWIGSINTDGSTYYATWAKGRFTISRTSTTVDLKITSPTTEDTATYFCARGYPGYITDSYYYFNIWGPGTLVTVS DVVLTQTPASVEAAVRGTVTIKCQASQSISSYLSWYQQKPGQPPKLLIYRASTLESGVPSRFKGSGSGTEFTLTITDLECADAATYYCQCTYGTFHSSGYGFGGGTGVVVKQSVEESGGRLVTPGTPLTLTCTVSGFSLSSYGMIWVRQAPGKGLEWIGSINTDGSTYYATWAKGRFTISRTSTTVDLKITSPTTEDTATYFCARGYPGYITDSYYYFNIWGPGTLVTVS DVVLTQTPASVEAAVRGTVTIKCQASQSISSYLSWYQQKPGQPPKLLIYRASTLESGVPSRFKGSGSGTEFTLTITDLECADAATYYCQCTYGTFHSSGYGFGGGTGVVVK10101H21H2VH CDR1VH CDR1aaaaGFSLSNYGGFS LS NYG1111VH CDR2VH CDR2aaaaIGTIGATIGTIGAT1212VH CDR3VH CDR3aaaaARGIYGDIYVYAFDIARGIYGDIYVYAFDI1313VL CDR1VL CDR1aaaaQSVRDNGDQSVRDNGD1414VL CDR2VL CDR2aaaaDVSDVS1515VL CDR3VL 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 CDR1VHCDR1aaaaGFSLSAYAGFSLSAYA2020VH CDR2VH CDR2aaaaISDSASTISDSAST21twenty oneVH CDR3VH CDR3aaaaARAYYVVDNDSPFNMARAYYVVDNDSPFNM22twenty twoVL CDR1VL CDR1aaaaENIYSSENIYSS23twenty threeVL CDR2VL CDR2aaaaAASAAS24twenty fourVL CDR3VLCDR3aaaaQSYYDTGRASFAQSYYDTGRASFA2525VHVHaaaaQSVEESGGRLVTPGTPLTLTCTVSGFSLSAYAMGWFRQAPGKGLEYIGIISDSASTFYATWAKGRFTISRTSSTMVDLKMTSPTTEDTATYFCARAYYVVDNDSPFNMWGPGTVVTVSQSVEESGGRLVTPGTPLTLTTCTVSGFSLSAYAMGWFRQAPGKGLEYIGIISDSASTFYATWAKGRFTISRTSSTMVDLKMTSPTTEDTATYFCARAYYVVDNDSPFNMWGPGTVVTVS2626VLVLaaaaVMTQTPSSVSAAVGGTVTINCQASENIYSSLAWYQQKPGQPPKLLIYAASKLESGVPSRFKGSRSETDFTLTISDLECDDAATYYCQSYYDTGRASFAFGGGTEVVVKVMTQTPSSVSAAVGGTVTINCQASENIYSSLAWYQQKPGQPPKLLIYAASKLESGVPSRFKGSRSETDFLTISDLECDDAATYYCQSYYDTGRASFAFGGGTEVVVK2727scfvscfvaaaaQSVEESGGRLVTPGTPLTLTCTVSGFSLSAYAMGWFRQAPGKGLEYIGIISDSASTFYATWAKGRFTISRTSSTMVDLKMTSPTTEDTATYFCARAYYVVDNDSPFNMWGPGTVVTVSVMTQTPSSVSAAVGGTVTINCQASENIYSSLAWYQQKPGQPPKLLIYAASKLESGVPSRFKGSRSETDFTLTISDLECDDAATYYCQSYYDTGRASFAFGGGTEVVVKQSVEESGGRLVTPGTPLTLTTCTVSGFSLSAYAMGWFRQAPGKGLEYIGIISDSASTFYATWAKGRFTISRTSSTMVDLKMTSPTTEDTATYFCARAYYVVDNDSPFNMWGPGTVVTVSVMTQTPSSVSAAVGGTVTINCQASENIYSSLAWYQQKPGQPPKLLIYAASKLESGVPSRFKGSRGTSETDFLTISDLEVDATYS

（6）CS1兔重组单克隆抗体的生产和鉴定(6) Production and identification of CS1 rabbit recombinant monoclonal antibody

将抗体的重轻链基因的表达质粒共转染入293细胞，37℃ 5% CO₂培养条件下培养72h，收集细胞上清，利用proteinA树脂进行抗体的纯化，纯化后的抗体进行SDS电泳鉴定，结果见图3。Co-transfect the expression plasmids of the heavy and light chain genes of the antibody into 293 cells, culture at 37°C and 5% CO₂ for 72 hours, collect the cell supernatant, use protein A resin to purify the antibody, and identify the purified antibody by SDS electrophoresis , the results are shown in Figure 3.

纯化后的抗体进行功能鉴定，具体如下：Purified antibodies were functionally identified as follows:

a) ELISA反应a) ELISA reaction

包被浓度为1μg/ml的CS1蛋白，100μl/孔，4℃孵育16h；次日弃掉包被液后用含1%BSA的PBS进行封闭，150μl/孔，37℃孵育1h。弃掉封闭液，加入不同倍比稀释的抗体，50μl/孔，37℃孵育1h。弃掉抗体，用含0.5%的Tween-20的PBS洗板5次，2min/次，最后加入稀释5000倍的羊抗兔IgG-HRP二抗，37℃孵育1h。弃掉二抗，用PBST洗板5次，2min/次。弃掉洗涤液，拍干，加入底物进行显色。ELISA检测结果见表2。CS1 protein was coated at a concentration of 1 μg/ml, 100 μl/well, and incubated at 4°C for 16 h; the next day, the coating solution was discarded and blocked with PBS containing 1% BSA, 150 μl/well, and incubated at 37°C for 1 h. Discard the blocking solution, add antibodies diluted in different ratios, 50 μl/well, and incubate at 37°C for 1 hour. Discard the antibody, wash theplate 5 times with PBS containing 0.5% Tween-20, 2min each time, and finally add goat anti-rabbit IgG-HRP secondary antibody diluted 5000 times, and incubate at 37°C for 1h. Discard the secondary antibody, wash theplate 5 times with PBST, 2min each time. Discard the wash solution, pat dry, and add substrate for color development. The results of the ELISA test are shown in Table 2.

表2. ELISA测试结果Table 2. ELISA test results

稀释倍数Dilution factor2B32B31D121D121H21H21K1KOverflowoverflowOverflowoverflow3.95423.95425K5K3.95193.9519Overflowoverflow3.8273.82725K25K2.90852.90853.44633.44632.38752.3875125K125K0.97950.97952.02472.02471.18441.1844625K625K0.2760.2760.52210.52210.32020.32023125k3125k0.16110.16110.20940.20940.15270.152715625k15625k0.10850.10850.12450.12450.11010.1101blankblank0.10320.10320.09110.09110.09780.0978

b) 基于流式结合力测定方法b) Flow-based binding assay method

用Raji细胞进行测试。即收集细胞于离心管中，采用无菌的PBS洗细胞两次，采用Fc受体封闭液进行细胞表面Fc受体的封闭，4℃孵育30min。离心收集细胞，用含0.5wt.%BSA的PBS洗细胞两次，加入不同浓度的抗体，4℃孵育30min。再用含0.5wt.%BSA的PBS洗细胞两次，最后加入羊抗兔IgG-488荧光二抗于4℃孵育30min。用含0.5wt.%BSA的PBS洗细胞两次后，加入200μl含0.5wt.%BSA的PBS重悬细胞，流式机器上机测试。流式测定结合力结果见图4。流式结合力分析显示所筛选的抗体具有不同的结合力。Tests were performed with Raji cells. That is, the cells were collected in a centrifuge tube, the cells were washed twice with sterile PBS, the Fc receptors on the cell surface were blocked with an Fc receptor blocking solution, and incubated at 4°C for 30 min. Cells were collected by centrifugation, washed twice with PBS containing 0.5wt.%BSA, added different concentrations of antibodies, and incubated at 4°C for 30min. Then wash the cells twice with PBS containing 0.5wt.%BSA, and finally add goat anti-rabbit IgG-488 fluorescent secondary antibody and incubate at 4°C for 30min. After washing the cells twice with PBS containing 0.5wt.%BSA, add 200μl of PBS containing 0.5wt.%BSA to resuspend the cells, and test on the flow cytometer. The results of flow cytometry binding force are shown in Figure 4. Flow cytometry binding analysis showed that the screened antibodies had different binding abilities.

c) 基于流式特异性测定方法c) Flow-based specific assay method

用293细胞转染CS1全长蛋白质粒进行测试。即收集转染细胞于离心管中，采用无菌的PBS洗细胞两次，采用Fc受体封闭液进行细胞表面Fc受体的封闭，4℃孵育30min。离心收集细胞，用含0.5wt.%BSA的PBS洗细胞两次，加入不同浓度的抗体，4℃孵育30min。再用含0.5wt.%BSA的PBS洗细胞两次，最后加入羊抗兔IgG-488荧光二抗于4℃孵育30min。用含0.5wt.%BSA的PBS洗细胞两次后，加入200μl含0.5wt.%BSA的PBS重悬细胞，流式机器上机测试。流式测试特异性结果见图5-图7。通过分析结果可见所筛选的抗体可以特异性识别细胞膜上CS1。293 cells were used to transfect CS1 full-length protein plasmid for testing. That is, collect the transfected cells in a centrifuge tube, wash the cells twice with sterile PBS, block the Fc receptors on the cell surface with Fc receptor blocking solution, and incubate at 4°C for 30 min. Cells were collected by centrifugation, washed twice with PBS containing 0.5wt.%BSA, added different concentrations of antibodies, and incubated at 4°C for 30min. Then wash the cells twice with PBS containing 0.5wt.%BSA, and finally add goat anti-rabbit IgG-488 fluorescent secondary antibody and incubate at 4°C for 30min. After washing the cells twice with PBS containing 0.5wt.%BSA, add 200μl of PBS containing 0.5wt.%BSA to resuspend the cells, and test on the flow cytometer. The specificity results of the flow cytometry test are shown in Figure 5-Figure 7. It can be seen from the analysis results that the screened antibody can specifically recognize CS1 on the cell membrane.

以上所述，仅为本发明较佳的具体实施方式，但本发明的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，可轻易想到的变化或替换，都应涵盖在本发明的保护范围内。The above is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any person skilled in the art can easily conceive of changes or modifications within the technical scope disclosed in the present invention. Replacement should be covered within the protection scope of the present invention.

序列表sequence listing

<110> 苏州缔码生物科技有限公司<110> Suzhou Dima Biotechnology Co., Ltd.

<120> 结合CS1蛋白兔重组单克隆抗体及应用<120> Rabbit Recombinant Monoclonal Antibody Binding to CS1 Protein and Its Application

<160> 27<160> 27

<170> SIPOSequenceListing 1.0<170> SIPOSequenceListing 1.0

<210> 1<210> 1

<211> 8<211> 8

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 1<400> 1

Gly Phe Ser Leu Ser Ser Tyr GlyGly Phe Ser Leu Ser Ser Tyr Gly

1 51 5

<210> 2<210> 2

<211> 7<211> 7

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 2<400> 2

Ile Asn Thr Asp Gly Ser ThrIle Asn Thr Asp Gly Ser Thr

1 51 5

<210> 3<210> 3

<211> 17<211> 17

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 3<400> 3

Ala Arg Gly Tyr Pro Gly Tyr Ile Thr Asp Ser Tyr Tyr Tyr Phe AsnAla Arg Gly Tyr Pro Gly Tyr Ile Thr Asp Ser Tyr Tyr Tyr Tyr Phe Asn

1 5 10 151 5 10 15

IleIle

<210> 4<210> 4

<211> 6<211> 6

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 4<400> 4

Gln Ser Ile Ser Ser TyrGln Ser Ile Ser Ser Tyr

1 51 5

<210> 5<210> 5

<211> 3<211> 3

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 5<400> 5

Arg Ala SerArg Ala Ser

11

<210> 6<210> 6

<211> 13<211> 13

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 6<400> 6

Gln Cys Thr Tyr Gly Thr Phe His Ser Ser Gly Tyr GlyGln Cys Thr Tyr Gly Thr Phe His Ser Ser Gly Tyr Gly

1 5 101 5 10

<210> 7<210> 7

<211> 119<211> 119

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 7<400> 7

Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr ProGln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro

1 5 10 151 5 10 15

Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr GlyLeu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Ser Tyr Gly

20 25 30 20 25 30

Met Ile Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile GlyMet Ile Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly

35 40 45 35 40 45

Ser Ile Asn Thr Asp Gly Ser Thr Tyr Tyr Ala Thr Trp Ala Lys GlySer Ile Asn Thr Asp Gly Ser Thr Tyr Tyr Ala Thr Trp Ala Lys Gly

50 55 60 50 55 60

Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Val Asp Leu Lys Ile ThrArg Phe Thr Ile Ser Arg Thr Ser Thr Thr Val Asp Leu Lys Ile Thr

65 70 75 8065 70 75 80

Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Gly TyrSer Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Gly Tyr

85 90 95 85 90 95

Pro Gly Tyr Ile Thr Asp Ser Tyr Tyr Tyr Phe Asn Ile Trp Gly ProPro Gly Tyr Ile Thr Asp Ser Tyr Tyr Tyr Phe Asn Ile Trp Gly Pro

100 105 110 100 105 110

Gly Thr Leu Val Thr Val SerGly Thr Leu Val Thr Val Ser

115 115

<210> 8<210> 8

<211> 111<211> 111

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 8<400> 8

Asp Val Val Leu Thr Gln Thr Pro Ala Ser Val Glu Ala Ala Val ArgAsp Val Val Leu Thr Gln Thr Pro Ala Ser Val Glu Ala Ala Val Arg

1 5 10 151 5 10 15

Gly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser TyrGly Thr Val Thr Ile Lys Cys Gln Ala Ser Gln Ser Ile Ser Ser Ser Tyr

20 25 30 20 25 30

Leu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu IleLeu Ser Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile

35 40 45 35 40 45

Tyr Arg Ala Ser Thr Leu Glu Ser Gly Val Pro Ser Arg Phe Lys GlyTyr Arg Ala Ser Thr Leu Glu Ser Gly Val Pro Ser Arg Phe Lys Gly

50 55 60 50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Thr Asp Leu Glu CysSer Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Thr Asp Leu Glu Cys

65 70 75 8065 70 75 80

Ala Asp Ala Ala Thr Tyr Tyr Cys Gln Cys Thr Tyr Gly Thr Phe HisAla Asp Ala Ala Thr Tyr Tyr Cys Gln Cys Thr Tyr Gly Thr Phe His

85 90 95 85 90 95

Ser Ser Gly Tyr Gly Phe Gly Gly Gly Thr Gly Val Val Val LysSer Ser Gly Tyr Gly Phe Gly Gly Gly Thr Gly Val Val Val Lys

100 105 110 100 105 110

<210> 9<210> 9

<211> 230<211> 230

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 9<400> 9

Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr ProGln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro

1 5 10 151 5 10 15

Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Tyr GlyLeu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ser Ser Tyr Gly

20 25 30 20 25 30

Met Ile Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile GlyMet Ile Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly

35 40 45 35 40 45

Ser Ile Asn Thr Asp Gly Ser Thr Tyr Tyr Ala Thr Trp Ala Lys GlySer Ile Asn Thr Asp Gly Ser Thr Tyr Tyr Ala Thr Trp Ala Lys Gly

50 55 60 50 55 60

Arg Phe Thr Ile Ser Arg Thr Ser Thr Thr Val Asp Leu Lys Ile ThrArg Phe Thr Ile Ser Arg Thr Ser Thr Thr Val Asp Leu Lys Ile Thr

65 70 75 8065 70 75 80

Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Gly TyrSer Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Gly Tyr

85 90 95 85 90 95

Pro Gly Tyr Ile Thr Asp Ser Tyr Tyr Tyr Phe Asn Ile Trp Gly ProPro Gly Tyr Ile Thr Asp Ser Tyr Tyr Tyr Phe Asn Ile Trp Gly Pro

100 105 110 100 105 110

Gly Thr Leu Val Thr Val Ser Asp Val Val Leu Thr Gln Thr Pro AlaGly Thr Leu Val Thr Val Ser Asp Val Val Leu Thr Gln Thr Pro Ala

115 120 125 115 120 125

Ser Val Glu Ala Ala Val Arg Gly Thr Val Thr Ile Lys Cys Gln AlaSer Val Glu Ala Ala Val Arg Gly Thr Val Thr Ile Lys Cys Gln Ala

130 135 140 130 135 140

Ser Gln Ser Ile Ser Ser Tyr Leu Ser Trp Tyr Gln Gln Lys Pro GlySer Gln Ser Ile Ser Ser Ser Tyr Leu Ser Trp Tyr Gln Gln Lys Pro Gly

145 150 155 160145 150 155 160

Gln Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Glu Ser GlyGln Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Thr Leu Glu Ser Gly

165 170 175 165 170 175

Val Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr LeuVal Pro Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu

180 185 190 180 185 190

Thr Ile Thr Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys GlnThr Ile Thr Asp Leu Glu Cys Ala Asp Ala Ala Thr Tyr Tyr Cys Gln

195 200 205 195 200 205

Cys Thr Tyr Gly Thr Phe His Ser Ser Gly Tyr Gly Phe Gly Gly GlyCys Thr Tyr Gly Thr Phe His Ser Ser Ser Gly Tyr Gly Phe Gly Gly Gly

210 215 220 210 215 220

Thr Gly Val Val Val LysThr Gly Val Val Val Lys

225 230225 230

<210> 10<210> 10

<211> 8<211> 8

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 10<400> 10

Gly Phe Ser Leu Ser Asn Tyr GlyGly Phe Ser Leu Ser Asn Tyr Gly

1 51 5

<210> 11<210> 11

<211> 7<211> 7

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 11<400> 11

Ile Gly Thr Ile Gly Ala ThrIle Gly Thr Ile Gly Ala Thr

1 51 5

<210> 12<210> 12

<211> 15<211> 15

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 12<400> 12

Ala Arg Gly Ile Tyr Gly Asp Ile Tyr Val Tyr Ala Phe Asp IleAla Arg Gly Ile Tyr Gly Asp Ile Tyr Val Tyr Ala Phe Asp Ile

1 5 10 151 5 10 15

<210> 13<210> 13

<211> 8<211> 8

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 13<400> 13

Gln Ser Val Arg Asp Asn Gly AspGln Ser Val Arg Asp Asn Gly Asp

1 51 5

<210> 14<210> 14

<211> 3<211> 3

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 14<400> 14

Asp Val SerAsp Val Ser

11

<210> 15<210> 15

<211> 12<211> 12

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 15<400> 15

Ala Gly Gly Tyr Ile Ala Gly Ser Asp Arg Trp ValAla Gly Gly Tyr Ile Ala Gly Ser Asp Arg Trp Val

1 5 101 5 10

<210> 16<210> 16

<211> 120<211> 120

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 16<400> 16

Gln Ser Val Glu Glu Ser Arg Gly Gly Leu Ile Lys Pro Thr Asp ThrGln Ser Val Glu Glu Ser Arg Gly Gly Leu Ile Lys Pro Thr Asp Thr

1 5 10 151 5 10 15

Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Asn Tyr GlyLeu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Asn Tyr Gly

20 25 30 20 25 30

Val Ser Trp Val Arg Gln Ala Pro Gly Asn Gly Leu Glu Tyr Ile GlyVal Ser Trp Val Arg Gln Ala Pro Gly Asn Gly Leu Glu Tyr Ile Gly

35 40 45 35 40 45

Phe Ile Gly Thr Ile Gly Ala Thr Leu Tyr Ala Asn Trp Ala Lys SerPhe Ile Gly Thr Ile Gly Ala Thr Leu Tyr Ala Asn Trp Ala Lys Ser

50 55 60 50 55 60

Arg Ser Thr Ile Thr Arg Asn Thr Asn Leu Asn Thr Val Thr Leu LysArg Ser Thr Ile Thr Arg Asn Thr Asn Leu Asn Thr Val Thr Leu Lys

65 70 75 8065 70 75 80

Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala ArgMet Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg

85 90 95 85 90 95

Gly Ile Tyr Gly Asp Ile Tyr Val Tyr Ala Phe Asp Ile Trp Gly ProGly Ile Tyr Gly Asp Ile Tyr Val Tyr Ala Phe Asp Ile Trp Gly Pro

100 105 110 100 105 110

Gly Thr Leu Val Thr Val Ser SerGly Thr Leu Val Thr Val Ser Ser

115 120 115 120

<210> 17<210> 17

<211> 112<211> 112

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 17<400> 17

Ala Ala Val Leu Thr Gln Thr Pro Ser Pro Val Ser Ala Ala Val GlyAla Ala Val Leu Thr Gln Thr Pro Ser Pro Val Ser Ala Ala Val Gly

1 5 10 151 5 10 15

Gly Thr Val Thr Ile Ser Cys Gln Ala Ser Gln Ser Val Arg Asp AsnGly Thr Val Thr Ile Ser Cys Gln Ala Ser Gln Ser Val Arg Asp Asn

20 25 30 20 25 30

Gly Asp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys LeuGly Asp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu

35 40 45 35 40 45

Leu Ile Tyr Asp Val Ser Ala Leu Ala Ser Gly Val Pro Ser Arg PheLeu Ile Tyr Asp Val Ser Ala Leu Ala Ser Gly Val Pro Ser Arg Phe

50 55 60 50 55 60

Lys Gly Arg Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Asp LeuLys Gly Arg Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Asp Leu

65 70 75 8065 70 75 80

Glu Cys Asp Asp Ala Ala Thr Tyr Ser Cys Ala Gly Gly Tyr Ile AlaGlu Cys Asp Asp Ala Ala Thr Tyr Ser Cys Ala Gly Gly Tyr Ile Ala

85 90 95 85 90 95

Gly Ser Asp Arg Trp Val Phe Gly Gly Gly Thr Glu Val Val Val LysGly Ser Asp Arg Trp Val Phe Gly Gly Gly Thr Glu Val Val Val Lys

100 105 110 100 105 110

<210> 18<210> 18

<211> 232<211> 232

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 18<400> 18

Gln Ser Val Glu Glu Ser Arg Gly Gly Leu Ile Lys Pro Thr Asp ThrGln Ser Val Glu Glu Ser Arg Gly Gly Leu Ile Lys Pro Thr Asp Thr

1 5 10 151 5 10 15

Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Asn Tyr GlyLeu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Asn Tyr Gly

20 25 30 20 25 30

Val Ser Trp Val Arg Gln Ala Pro Gly Asn Gly Leu Glu Tyr Ile GlyVal Ser Trp Val Arg Gln Ala Pro Gly Asn Gly Leu Glu Tyr Ile Gly

35 40 45 35 40 45

Phe Ile Gly Thr Ile Gly Ala Thr Leu Tyr Ala Asn Trp Ala Lys SerPhe Ile Gly Thr Ile Gly Ala Thr Leu Tyr Ala Asn Trp Ala Lys Ser

50 55 60 50 55 60

Arg Ser Thr Ile Thr Arg Asn Thr Asn Leu Asn Thr Val Thr Leu LysArg Ser Thr Ile Thr Arg Asn Thr Asn Leu Asn Thr Val Thr Leu Lys

65 70 75 8065 70 75 80

Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala ArgMet Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg

85 90 95 85 90 95

Gly Ile Tyr Gly Asp Ile Tyr Val Tyr Ala Phe Asp Ile Trp Gly ProGly Ile Tyr Gly Asp Ile Tyr Val Tyr Ala Phe Asp Ile Trp Gly Pro

100 105 110 100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ala Val Leu Thr Gln Thr ProGly Thr Leu Val Thr Val Ser Ser Ala Ala Val Leu Thr Gln Thr Pro

115 120 125 115 120 125

Ser Pro Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Ser Cys GlnSer Pro Val Ser Ala Ala Val Gly Gly Thr Val Thr Ile Ser Cys Gln

130 135 140 130 135 140

Ala Ser Gln Ser Val Arg Asp Asn Gly Asp Leu Ala Trp Tyr Gln GlnAla Ser Gln Ser Val Arg Asp Asn Gly Asp Leu Ala Trp Tyr Gln Gln

145 150 155 160145 150 155 160

Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Asp Val Ser Ala LeuLys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Asp Val Ser Ala Leu

165 170 175 165 170 175

Ala Ser Gly Val Pro Ser Arg Phe Lys Gly Arg Gly Ser Gly Thr GlnAla Ser Gly Val Pro Ser Arg Phe Lys Gly Arg Gly Ser Gly Thr Gln

180 185 190 180 185 190

Phe Thr Leu Thr Ile Ser Asp Leu Glu Cys Asp Asp Ala Ala Thr TyrPhe Thr Leu Thr Ile Ser Asp Leu Glu Cys Asp Asp Ala Ala Thr Tyr

195 200 205 195 200 205

Ser Cys Ala Gly Gly Tyr Ile Ala Gly Ser Asp Arg Trp Val Phe GlySer Cys Ala Gly Gly Tyr Ile Ala Gly Ser Asp Arg Trp Val Phe Gly

210 215 220 210 215 220

Gly Gly Thr Glu Val Val Val LysGly Gly Thr Glu Val Val Val Lys

225 230225 230

<210> 19<210> 19

<211> 8<211> 8

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 19<400> 19

Gly Phe Ser Leu Ser Ala Tyr AlaGly Phe Ser Leu Ser Ala Tyr Ala

1 51 5

<210> 20<210> 20

<211> 7<211> 7

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 20<400> 20

Ile Ser Asp Ser Ala Ser ThrIle Ser Asp Ser Ala Ser Thr

1 51 5

<210> 21<210> 21

<211> 15<211> 15

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 21<400> 21

Ala Arg Ala Tyr Tyr Val Val Asp Asn Asp Ser Pro Phe Asn MetAla Arg Ala Tyr Tyr Val Val Asp Asn Asp Ser Pro Phe Asn Met

1 5 10 151 5 10 15

<210> 22<210> 22

<211> 6<211> 6

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 22<400> 22

Glu Asn Ile Tyr Ser SerGlu Asn Ile Tyr Ser Ser

1 51 5

<210> 23<210> 23

<211> 3<211> 3

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 23<400> 23

Ala Ala SerAla Ala Ser

11

<210> 24<210> 24

<211> 12<211> 12

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 24<400> 24

Gln Ser Tyr Tyr Asp Thr Gly Arg Ala Ser Phe AlaGln Ser Tyr Tyr Asp Thr Gly Arg Ala Ser Phe Ala

1 5 101 5 10

<210> 25<210> 25

<211> 118<211> 118

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 25<400> 25

Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr ProGln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro

1 5 10 151 5 10 15

Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ala Tyr AlaLeu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ala Tyr Ala

20 25 30 20 25 30

Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile GlyMet Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile Gly

35 40 45 35 40 45

Ile Ile Ser Asp Ser Ala Ser Thr Phe Tyr Ala Thr Trp Ala Lys GlyIle Ile Ser Asp Ser Ala Ser Thr Phe Tyr Ala Thr Trp Ala Lys Gly

50 55 60 50 55 60

Arg Phe Thr Ile Ser Arg Thr Ser Ser Thr Met Val Asp Leu Lys MetArg Phe Thr Ile Ser Arg Thr Ser Ser Thr Met Val Asp Leu Lys Met

65 70 75 8065 70 75 80

Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg AlaThr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Ala

85 90 95 85 90 95

Tyr Tyr Val Val Asp Asn Asp Ser Pro Phe Asn Met Trp Gly Pro GlyTyr Tyr Val Val Asp Asn Asp Ser Pro Phe Asn Met Trp Gly Pro Gly

100 105 110 100 105 110

Thr Val Val Thr Val SerThr Val Val Thr Val Ser

115 115

<210> 26<210> 26

<211> 108<211> 108

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 26<400> 26

Val Met Thr Gln Thr Pro Ser Ser Val Ser Ala Ala Val Gly Gly ThrVal Met Thr Gln Thr Pro Ser Ser Val Ser Ala Ala Val Gly Gly Thr

1 5 10 151 5 10 15

Val Thr Ile Asn Cys Gln Ala Ser Glu Asn Ile Tyr Ser Ser Leu AlaVal Thr Ile Asn Cys Gln Ala Ser Glu Asn Ile Tyr Ser Ser Leu Ala

20 25 30 20 25 30

Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr AlaTrp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Ala

35 40 45 35 40 45

Ala Ser Lys Leu Glu Ser Gly Val Pro Ser Arg Phe Lys Gly Ser ArgAla Ser Lys Leu Glu Ser Gly Val Pro Ser Arg Phe Lys Gly Ser Arg

50 55 60 50 55 60

Ser Glu Thr Asp Phe Thr Leu Thr Ile Ser Asp Leu Glu Cys Asp AspSer Glu Thr Asp Phe Thr Leu Thr Ile Ser Asp Leu Glu Cys Asp Asp

65 70 75 8065 70 75 80

Ala Ala Thr Tyr Tyr Cys Gln Ser Tyr Tyr Asp Thr Gly Arg Ala SerAla Ala Thr Tyr Tyr Cys Gln Ser Tyr Tyr Asp Thr Gly Arg Ala Ser

85 90 95 85 90 95

Phe Ala Phe Gly Gly Gly Thr Glu Val Val Val LysPhe Ala Phe Gly Gly Gly Thr Glu Val Val Val Lys

100 105 100 105

<210> 27<210> 27

<211> 226<211> 226

<212> PRT<212> PRT

<213> 人工序列(Artificial Sequence)<213> Artificial Sequence

<400> 27<400> 27

Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr ProGln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro

1 5 10 151 5 10 15

Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ala Tyr AlaLeu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Ala Tyr Ala

20 25 30 20 25 30

Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile GlyMet Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile Gly

35 40 45 35 40 45

Ile Ile Ser Asp Ser Ala Ser Thr Phe Tyr Ala Thr Trp Ala Lys GlyIle Ile Ser Asp Ser Ala Ser Thr Phe Tyr Ala Thr Trp Ala Lys Gly

50 55 60 50 55 60

Arg Phe Thr Ile Ser Arg Thr Ser Ser Thr Met Val Asp Leu Lys MetArg Phe Thr Ile Ser Arg Thr Ser Ser Thr Met Val Asp Leu Lys Met

65 70 75 8065 70 75 80

Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg AlaThr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Ala

85 90 95 85 90 95

Tyr Tyr Val Val Asp Asn Asp Ser Pro Phe Asn Met Trp Gly Pro GlyTyr Tyr Val Val Asp Asn Asp Ser Pro Phe Asn Met Trp Gly Pro Gly

100 105 110 100 105 110

Thr Val Val Thr Val Ser Val Met Thr Gln Thr Pro Ser Ser Val SerThr Val Val Thr Val Ser Val Met Thr Gln Thr Pro Ser Ser Val Ser

115 120 125 115 120 125

Ala Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser Glu AsnAla Ala Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser Glu Asn

130 135 140 130 135 140

Ile Tyr Ser Ser Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro ProIle Tyr Ser Ser Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro

145 150 155 160145 150 155 160

Lys Leu Leu Ile Tyr Ala Ala Ser Lys Leu Glu Ser Gly Val Pro SerLys Leu Leu Ile Tyr Ala Ala Ser Lys Leu Glu Ser Gly Val Pro Ser

165 170 175 165 170 175

Arg Phe Lys Gly Ser Arg Ser Glu Thr Asp Phe Thr Leu Thr Ile SerArg Phe Lys Gly Ser Arg Ser Glu Thr Asp Phe Thr Leu Thr Ile Ser

180 185 190 180 185 190

Asp Leu Glu Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Ser Tyr TyrAsp Leu Glu Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Ser Tyr Tyr

195 200 205 195 200 205

Asp Thr Gly Arg Ala Ser Phe Ala Phe Gly Gly Gly Thr Glu Val ValAsp Thr Gly Arg Ala Ser Phe Ala Phe Gly Gly Gly Thr Glu Val Val

210 215 220 210 215 220

Val LysVal Lys

225225

Claims (10)

1. A CS1 protein-binding rabbit recombinant monoclonal antibody, which is characterized in that: one or more of the following rabbit recombinant monoclonal antibodies:

rabbit recombinant monoclonal antibody designated 1D 12: the amino acid sequences of the heavy chain complementarity determining regions CDR1, CDR2 and CDR3 are respectively the amino acid sequences shown in SEQ ID NO. 1, SEQ ID NO. 2 and SEQ ID NO. 3; and the amino acid sequences of the light chain complementarity determining regions CDR1, CDR2 and CDR3 are respectively the amino acid sequences shown in SEQ ID NO. 4, SEQ ID NO. 5 and SEQ ID NO. 6;

rabbit recombinant monoclonal antibody designated 1H 2: the amino acid sequences of the heavy chain complementary determining regions CDR1, CDR2 and CDR3 are respectively the amino acid sequences shown in SEQ ID NO. 10, SEQ ID NO. 11 and SEQ ID NO. 12, and the amino acid sequences of the light chain complementary determining regions CDR1, CDR2 and CDR3 are respectively the amino acid sequences shown in SEQ ID NO. 13, SEQ ID NO. 14 and SEQ ID NO. 15;

the amino acid sequences of the heavy chain complementary determining regions CDR1, CDR2 and CDR3 of the rabbit recombinant monoclonal antibody named as 2B3 are respectively the amino acid sequences shown in SEQ ID NO. 19, SEQ ID NO. 20 and SEQ ID NO. 21, and the amino acid sequences of the light chain complementary determining regions CDR1, CDR2 and CDR3 are respectively the amino acid sequences shown in SEQ ID NO. 22, SEQ ID NO. 23 and SEQ ID NO. 24.

2. The CS1 protein-binding rabbit recombinant monoclonal antibody according to claim 1, wherein:

the heavy chain variable region sequence of the rabbit recombinant monoclonal antibody named as 1D12 is an amino acid sequence shown by SEQ ID NO. 7, and the light chain variable region sequence is an amino acid sequence shown by SEQ ID NO. 8;

the rabbit recombinant monoclonal antibody named as 1H2 has a heavy chain variable region sequence of an amino acid sequence shown in SEQ ID NO. 16 and a light chain variable region sequence of an amino acid sequence shown in SEQ ID NO. 17;

the rabbit recombinant monoclonal antibody named as 2B3 has the heavy chain variable region sequence as shown in SEQ ID No. 25 and the light chain variable region sequence as shown in SEQ ID No. 26.

3. The rabbit recombinant monoclonal antibody that binds to CS1 protein according to claim 1 or 2, characterized in that:

the SCFV sequence of the rabbit recombinant monoclonal antibody named as 1D12 is an amino acid sequence shown in SEQ ID NO. 9;

the SCFV sequence of the rabbit recombinant monoclonal antibody named as 1H2 is an amino acid sequence shown in SEQ ID NO. 18;

the SCFV sequence of the rabbit recombinant monoclonal antibody named 2B3 is an amino acid sequence shown in SEQ ID NO. 27.

4. The rabbit recombinant monoclonal antibody that binds to CS1 protein according to claim 1, characterized in that: the light chain constant region of the rabbit recombinant monoclonal antibody is a kappa chain, and the heavy chain constant region is an IgG type.

5. A nucleic acid molecule, characterized in that: comprising a nucleic acid sequence capable of encoding a heavy chain complementarity determining region or a light chain complementarity determining region of a rabbit recombinant monoclonal antibody that binds to a CS1 protein according to any one of claims 1-4.

6. A carrier, characterized by: comprising the nucleic acid molecule of claim 5.

7. A host cell, characterized in that: the host cell comprising the rabbit recombinant monoclonal antibody binding to CS1 protein according to any one of claims 1 to 4, the nucleic acid molecule of claim 5 or the vector of claim 6.

8. A conjugate, characterized by: comprising an antibody according to any one of claims 1 to 4.

9. A pharmaceutical composition characterized by: contains a main component and an auxiliary component, wherein the main component contains one or more of the rabbit recombinant monoclonal antibody which is combined with the CS1 protein and is described in any one of claim 1 to 4, the nucleic acid molecule described in claim 5, the carrier described in claim 6, the host cell described in claim 7, the conjugate described in claim 8, and the auxiliary component is selected from pharmaceutically acceptable carriers or excipients, and other optional bioactive substances.

10. Use of a rabbit recombinant monoclonal antibody that binds to a CS1 protein according to any one of claims 1 to 4, a nucleic acid molecule according to claim 5, a vector according to claim 6, a host cell according to claim 7, or a conjugate according to claim 8 for the preparation of a medicament or a detection reagent for the treatment of a disease.

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