Anti-B7-H3 antibody and methods of use thereof
The present disclosure provides antibodies that specifically bind to B7-H3. The antibodies find use in a variety of treatment, diagnostic, and monitoring applications, which are also described. The present disclosure provides antibodies that specifically bind to B7-H3. A subject antibody specifically binds B7-H3 from humans and other mammals, e.g., monkey and mouse.
1. An antibody that binds to B7-H3, wherein the antibody comprises:
a variable domain comprising:
i. heavy chain CDR1, CDR2 and CDR3 regions that are identical to the heavy chain CDR1, CDR2 and CDR3 regions of SEQ ID NO: 39; and
ii. light chain CDR1, CDR2 and CDR3 regions that are identical to the light chain CDR1, CDR2 and CDR3 regions of SEQ ID NO: 93,
wherein SEQ ID NOS: 39 and 93 are the respective heavy and light chains of antibody 40633p1.1.G7.
2. The antibody of claim 1 , wherein the antibody comprises:
a heavy chain variable domain comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 39; and
a light chain variable domain comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 93.
3. The antibody of claim 1 , wherein the heavy chain variable domain and the light chain variable domain are present in separate polypeptides.
4. The antibody of claim 1 , wherein the heavy chain variable domain and the light chain variable domain are present in a single polypeptide.
5. The antibody of claim 1 , wherein the antibody binds B7-H3 with an affinity in the range of 10 7 M −1 to 10 12 M −1 .
6. The antibody of claim 1 , wherein the antibody comprises a covalently linked non-peptide synthetic polymer.
7. The antibody of claim 6 , wherein the synthetic polymer is poly(ethylene glycol) polymer.
8. The antibody of claim 1 , wherein the antibody comprises a covalently linked lipid or fatty acid moiety.
9. The antibody of claim 1 , wherein the antibody comprises a covalently linked polysaccharide or carbohydrate moiety.
10. The antibody of claim 1 , wherein the antibody is a single chain Fv (scFv) antibody.
11. The antibody of claim 10 , wherein the scFv is multimerized.
12. A pharmaceutical composition comprising:
a) the antibody of claim 1 ; and
b) a pharmaceutically acceptable carrier.
13. The pharmaceutical composition of claim 12 , wherein the antibody is encapsulated in a liposome.
14. A method for inhibiting B7-H3, comprising contacting a cell comprising B7-H3 with an antibody of claim 1 .
15. A method of inhibiting B7-H3 in a subject, comprising administering to the subject an effective amount of the antibody of claim 1 .
16. A method of treating cancer, comprising administering to a cancer patient an effective amount of the antibody of claim 1 .
17. The method of claim 16 , wherein the cancer is multiple myeloma.
18. The method of claim 16 , wherein the cancer is melanoma of the skin, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancer, or Hodgkin lymphoma.
19. The method of claim 18 , wherein the patient is also being treated or has been treated with an immune checkpoint inhibitor.
20. The method of claim 19 , wherein the immune checkpoint inhibitor is a PD-1/PD-L1 inhibitor.
21. The antibody of claim 1 , wherein the antibody comprises:
a heavy chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 39; and
a light chain variable domain comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 93.