Anti-CD73 anti-PD-L1 bispecific antibodies
Provided are bispecific antibodies capable of binding to human CD73 protein and human PD-L1 protein. These bispecific antibodies are effective in treating cancer.
1. A bispecific antibody comprising an anti-CD73 portion and an anti-PD-L1 portion,
wherein the anti-CD73 portion has binding specificity to a human CD73 protein and comprises a heavy chain variable region comprising a CDRH1 comprising the amino acid sequence of SEQ ID NO:1, a CDRH2 comprising the amino acid sequence of SEQ ID NO:2, and a CDRH3 comprising the amino acid sequence of SEQ ID NO:3, and a light chain variable region comprising a CDRL1 comprising the amino acid sequence of SEQ ID NO:4, a CDRL2 comprising the amino acid sequence of SEQ ID NO:5, and a CDRL3 comprising the amino acid sequence of SEQ ID NO:6, and
wherein the anti-PD-L1 portion has binding specificity to a human PD-L1 protein and comprises a heavy chain variable region comprising a CDRH1 comprising the amino acid sequence of SEQ ID NO:7, a CDRH2 comprising the amino acid sequence of SEQ ID NO:8, and a CDRH3 comprising the amino acid sequence of SEQ ID NO:9, and a light chain variable region comprising a CDRL1 comprising the amino acid sequence of SEQ ID NO:10, a CDRL2 comprising the amino acid sequence of SEQ ID NO:11, and a CDRL3 comprising the amino acid sequence of SEQ ID NO:12.
2. The bispecific antibody of claim 1 , wherein the anti-CD73 portion comprises a Fab fragment.
3. The bispecific antibody of claim 2 , wherein the anti-PD-L1 portion comprises a single-chain variable fragment (scFv).
4. The bispecific antibody of claim 1 , wherein the anti-CD73 portion comprises a single-chain variable fragment (scFv).
5. The bispecific antibody of claim 4 , wherein the anti-PD-L1 portion comprises a Fab fragment.
6. The bispecific antibody of claim 3 , comprising a first peptide linker between the Fab and the scFv.
7. The bispecific antibody of claim 6 , wherein the first peptide linker comprises SEQ ID NO:13 or SEQ ID NO:14.
8. The bispecific antibody of claim 6 , wherein the scFv comprises a second peptide linker between the heavy chain variable region and the light chain variable region.
9. The bispecific antibody of claim 8 , wherein the second peptide linker comprises SEQ ID NO:13 or SEQ ID NO:14.
10. The bispecific antibody of claim 1 , wherein the anti-CD73 portion and the anti-PD-L1 portion form a heterodimer.
11. The bispecific antibody of claim 10 , wherein the anti-CD73 portion comprises a Fab fragment, or a single-chain variable fragment (scFv).
12. The bispecific antibody of claim 10 , wherein the anti-PD-L1 portion comprises a Fab fragment, or a single-chain variable fragment (scFv).
13. The bispecific antibody of claim 12 , wherein the anti-CD73 and the anti-PD-L1 portions each comprises a Fab fragment.
14. The bispecific antibody of claim 1 , further comprising a Fc fragment.
15. The bispecific antibody of claim 1 , wherein the heavy chain variable region of the anti-CD73 portion comprises the amino acid sequence of SEQ ID NO:21 and the light chain variable region of the anti-CD73 portion comprises the amino acid sequence of SEQ ID NO:22.
16. The bispecific antibody of claim 1 , wherein the heavy chain variable region of the anti-PD-L1 portion comprises the amino acid sequence of SEQ ID NO:23 and the light chain variable region of the anti-PD-L1 portion comprises the amino acid sequence of SEQ ID NO:24.
17. The bispecific antibody of claim 1 , comprising two heavy chains each comprising the amino acid sequence of SEQ ID NO:15 and two light chains each comprising the amino acid sequence of SEQ ID NO:16.
18. The bispecific antibody of claim 1 , comprising two heavy chains each comprising the amino acid sequence of SEQ ID NO:17 and two light chains each comprising the amino acid sequence of SEQ ID NO:16.
19. The bispecific antibody of claim 1 , comprising two heavy chains each comprising the amino acid sequence of SEQ ID NO:18 and two light chains each comprising the amino acid sequence of SEQ ID NO:19.
20. The bispecific antibody of claim 1 , comprising two heavy chains each comprising the amino acid sequence of SEQ ID NO:20 and two light chains each comprising the amino acid sequence of SEQ ID NO:19.
21. A method of treating cancer in a patient in need thereof, comprising administering to the patient the antibody of claim 1 .
22. The method of claim 21 , wherein the cancer is selected from the group consisting of bladder cancer, breast cancer, colorectal cancer, endometrial cancer, esophageal cancer, head and neck cancer, kidney cancer, leukemia, liver cancer, lung cancer, lymphoma, melanoma, pancreatic cancer, prostate cancer, and thyroid cancer.
23. A method of treating cancer in a patient in need thereof, comprising:
(a) treating a T cell, in vitro, with the antibody of claim 1 ; and
(b) administering the treated T cell to the patient.