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CN-121342988-B - Antibody CM0735 and uses thereof

CN121342988BCN 121342988 BCN121342988 BCN 121342988BCN-121342988-B

Abstract

The invention discloses an antibody CM0735 and application thereof, wherein the antibody CM0735 is an antibody targeting B7-H3 protein, HCDR1-3 in a heavy chain variable region is respectively shown as SEQ ID NO. 1-3, LCDR1-3 in a light chain variable region is respectively shown as SEQ ID NO. 5-7, and the antibody CM0735 has higher binding activity on B7-H3, can be used for detecting and treating B7-H3 abnormal expression diseases, and has important significance for preventing and controlling B7-H3 abnormal expression related diseases.

Inventors

  • XIE LU
  • TANG XIAODONG
  • REN TINGTING
  • ZHAO YUWEI
  • XU JIE
  • YU YIYANG

Assignees

  • 北京大学人民医院

Dates

Publication Date
20260512
Application Date
20251110

Claims (15)

  1. 1. A B7-H3 antibody or antigen-binding fragment thereof, wherein the B7-H3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 and a light chain variable region comprising LCDR1, LCDR2 and LCDR3; The amino acid sequences of the HCDR1, the HCDR2 and the HCDR3 are respectively shown in SEQ ID NO. 1,2 and 3, and the amino acid sequences of the LCDR1, the LCDR2 and the LCDR3 are respectively shown in SEQ ID NO. 5, 6 and 7.
  2. 2. The B7-H3 antibody or antigen-binding fragment thereof according to claim 1, wherein the heavy chain variable region of the B7-H3 antibody or antigen-binding fragment thereof comprises the amino acid sequence shown in SEQ ID No.4 or an amino acid sequence having at least 75% identity to SEQ ID No.4 and the light chain variable region comprises the amino acid sequence shown in SEQ ID No. 8 or an amino acid sequence having at least 75% identity to SEQ ID No. 8.
  3. 3. A polynucleotide molecule encoding the B7-H3 antibody or antigen-binding fragment thereof according to any one of claims 1 or 2.
  4. 4. A carrier, characterized in that, the vector comprises the polynucleotide molecule of claim 3.
  5. 5. An engineered host cell comprising the polynucleotide molecule of claim 3 or the vector of claim 4.
  6. 6. The engineered host cell of claim 5, wherein the engineered host cell comprises a prokaryotic cell, a eukaryotic cell.
  7. 7. A population of engineered host cells, wherein the population of engineered host cells comprises the engineered host cell of any one of claims 5 or 6, as well as other host cells.
  8. 8. An antibody derivative of a B7-H3 antibody or antigen-binding fragment thereof, comprising a complex of a B7-H3 antibody or antigen-binding fragment thereof as defined in any one of claims 1 or 2 coupled directly or indirectly to a detectable label.
  9. 9. The antibody derivative of claim 8, wherein the detectable label comprises a fluorescent dye, an enzyme, a chemiluminescent label, an electron dense reagent, a colored particle, biotin, or digoxin.
  10. 10. An assay reagent or assay product comprising the B7-H3 antibody or antigen-binding fragment thereof of any one of claims 1 or2 or the antibody derivative of any one of claims 8 or 9.
  11. 11. The detection reagent or detection product according to claim 10, wherein the product comprises a kit, a chip, a test strip.
  12. 12. A pharmaceutical composition for the treatment of a disease or disorder of abnormal B7-H3 expression, characterized in that the pharmaceutical composition comprises a B7-H3 antibody or antigen-binding fragment thereof as defined in any one of claims 1 or 2 or an antibody derivative as defined in any one of claims 8 or 9.
  13. 13. The pharmaceutical composition of claim 12, wherein the disease or disorder of abnormal B7-H3 expression comprises osteosarcoma, glioma, melanoma, hematological malignancy, prostate cancer, esophageal cancer, cervical cancer, ovarian cancer, colorectal cancer, breast cancer, or lung cancer.
  14. 14. A method of any one of: 1) A method of preparing the B7-H3 antibody or antigen-binding fragment thereof of any one of claims 1 or 2, comprising the steps of culturing the engineered host cell of any one of claims 5 or 6 or the population of engineered host cells of claim 7, and isolating the B7-H3 antibody or antigen-binding fragment thereof from the culture; 2) A method for non-diagnostic, non-therapeutic detection of B7-H3 or a fragment thereof in a test sample, the method comprising the steps of contacting the test sample with a B7-H3 antibody or an antigen binding fragment thereof as defined in any one of claims 1 or 2, an antibody derivative as defined in any one of claims 8 or 9 or a detection reagent or detection product as defined in any one of claims 10 or 11, detecting the formation of a corresponding antibody-antigen complex; 3) A method of making the engineered host cell of any one of claims 5 or 6 or the population of engineered host cells of claim 7, the method comprising the step of introducing the polynucleotide molecule of claim 3 or the vector of claim 4 into a host cell; 4) A method of inhibiting B7-H3 activity in a sample in vitro, comprising contacting the sample with the B7-H3 antibody or antigen binding fragment thereof of any one of claims 1 or 2.
  15. 15. Any of the following applications: 1) Use of the B7-H3 antibody or antigen binding fragment thereof of any one of claims 1 or 2, the polynucleotide molecule of claim 3, the vector of claim 4, the engineered host cell of any one of claims 5 or 6, the population of engineered host cells of claim 7, or the antibody derivative of any one of claims 8 or 9 in the preparation of a detection reagent or detection product for detecting B7-H3; 2) Use of the B7-H3 antibody or antigen binding fragment thereof of any one of claims 1 or 2, the polynucleotide molecule of claim 3, the vector of claim 4, the engineered host cell of any one of claims 5 or 6, the population of engineered host cells of claim 7, the antibody derivative of any one of claims 8 or 9, or the detection reagent or detection product of any one of claims 10 or 11 for the preparation of a diagnostic product for diagnosing or aiding in the diagnosis of a B7-H3 abnormal expression disease; 3) Use of the B7-H3 antibody or antigen binding fragment thereof of any one of claims 1 or 2, the polynucleotide molecule of claim 3, the vector of claim 4, the engineered host cell of any one of claims 5 or 6, the population of engineered host cells of claim 7, the antibody derivative of any one of claims 8 or 9, or the detection reagent or detection product of any one of claims 10 or 11 for the detection of B7-H3 at a non-diagnostic, non-therapeutic destination.

Description

Antibody CM0735 and uses thereof Technical Field The invention belongs to the technical field of biological medicine, and particularly relates to an antibody CM0735 and application thereof. Background B7-H3 is one of the members of the B7 family of costimulatory mediators, and was first discovered in 2001 in cDNA libraries derived from human dendritic cells, again designated CD276, belonging to the immunoglobulin superfamily. B7-H3 has two isomers, namely 2 IgB-H3 with a double-region structure and 4 IgB-H3 (IgV-IgC-IgV-IgC) with a four-region structure, both of which are expressed in human tissues, and mainly the latter, 4IgB7-H3 is only found in human bodies, only 2IgB7-H3 is found in mouse tissues, and no functional difference is found at present. Currently, B7-H3 is found to be widely expressed in the biological world, and in addition to mammals such as humans, its expression is found to exist even in the body of lower vertebrates such as fish, and B7-H3 sequences are highly similar among different species. B7-H3 is widely expressed in many tissues of human body, and researchers find out the expression of its protein in various organs such as circulatory system, reproductive system, digestive system, endocrine system, and motor system of human body, but the protein expression of B7-H3 is limited and maintained at low level. Under normal steady state, the B7-H3 protein is only expressed at low levels in tissues such as liver, lung, breast, prostate, testis, placenta, etc. With further penetration of B7-H3 research, researchers found that B7-H3 protein exhibited high expression in cancerous tissues of many tumor patients, such as osteosarcoma, prostate cancer, colorectal cancer, cervical cancer, and the like. By detection methods such as immunohistochemistry, B7-H3 was found to be highly expressed on the surface of tumor cells and in the cytoplasm. Several studies have shown that B7-H3 may play a role in promoting tumorigenesis. Therefore, the development and research of antibodies targeting B7-H3 have important clinical and scientific values. There is still a strong need in the art to develop an antibody product with better affinity and specificity for B7-H3. Disclosure of Invention In view of this, the present invention has been made in order to make up for the deficiencies of the prior art. The first aspect of the present invention provides a B7-H3 antibody or antigen-binding fragment thereof, the B7-H3 antibody or antigen-binding fragment thereof comprising a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 and a light chain variable region comprising LCDR1, LCDR2 and LCDR3; The amino acid sequences of the HCDR1, the HCDR2 and the HCDR3 are respectively shown in SEQ ID NO. 1,2 and 3, and the amino acid sequences of the LCDR1, the LCDR2 and the LCDR3 are respectively shown in SEQ ID NO. 5, 6 and 7. Further, the heavy chain variable region of the B7-H3 antibody or antigen binding fragment thereof comprises the amino acid sequence shown in SEQ ID NO. 4 or an amino acid sequence having at least 75% identity to SEQ ID NO. 4, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO. 8 or an amino acid sequence having at least 75% identity to SEQ ID NO. 8. In the present invention, the B7-H3 antibody or antigen-binding fragment thereof may be a monoclonal antibody, a domain antibody, a single chain (scFv), a Fab fragment, a F (ab') 2 fragment multispecific antibody, a single domain heavy chain antibody, or a single domain light chain antibody. In some embodiments, such antibodies or antigen binding fragments thereof that bind B7-H3 protein are mouse, other rodent, chimeric, humanized or fully human monoclonal antibodies. "Complementarity determining regions" or "CDR regions" or "CDRs" or "hypervariable regions" are regions of an antibody variable region that are highly variable in sequence and form structurally defined loops ("hypervariable loops") and/or contain antigen-contacting residues ("antigen-contacting points"). CDRs are mainly responsible for binding to the epitope. Based on the variable region amino acid sequences contained in a given B7-H3 antibody or antigen binding fragment thereof of the present invention, one skilled in the art can routinely determine the CDRs contained therein. For example, the CDRs in the variable region amino acid sequence are defined using the Kabat protocol, the AbM protocol, the Chothia protocol, or the Contact protocol. When referring to defining antibodies with specific CDR sequences as defined herein, the scope of the antibodies also encompasses antibodies whose variable region sequences comprise the specific CDR sequences, but whose purported CDR boundaries differ from the specific CDR boundaries defined herein by the application of different schemes (e.g., different assignment system rules or combinations). The CDRs of the antibodies of the invention can be evaluated manually to determine boundaries according to any prot