Anti-TIM-3 antibodies and methods of use thereof
The instant disclosure provides antibodies that specifically bind to TIM-3 (e.g., human TIM-3) and antagonize TIM-3 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.
1. An isolated antibody that specifically binds to human TIM-3, comprising a heavy chain variable region comprising complementarity determining regions CDRH1, CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the amino acid sequences of SEQ ID NOs: 5, 2, and 3, respectively; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 46.
2. The isolated antibody of claim 1 , wherein the amino acid sequence of the light chain variable region consists of the amino acid sequence of SEQ ID NO: 46.
3. The isolated antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 69.
4. The isolated antibody of claim 3 , wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 69.
5. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier or excipient.
6. A pharmaceutical composition comprising the antibody of claim 2 and a pharmaceutically acceptable carrier or excipient.
7. A pharmaceutical composition comprising the antibody of claim 3 and a pharmaceutically acceptable carrier or excipient.
8. A pharmaceutical composition comprising the antibody of claim 4 and a pharmaceutically acceptable carrier or excipient.
9. An isolated antibody that specifically binds to human TIM-3, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 28; and a light chain variable region comprising complementarity determining regions CDRL1, CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 comprise the amino acid sequences of SEQ ID NOs: 14, 21, and 22, respectively.
10. The isolated antibody of claim 9 , wherein the amino acid sequence of the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 28.
11. The isolated antibody of claim 9 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 61.
12. The isolated antibody of claim 11 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 61.
13. A pharmaceutical composition comprising the antibody of claim 9 and a pharmaceutically acceptable carrier or excipient.
14. A pharmaceutical composition comprising the antibody of claim 10 and a pharmaceutically acceptable carrier or excipient.
15. A pharmaceutical composition comprising the antibody of claim 11 and a pharmaceutically acceptable carrier or excipient.
16. A pharmaceutical composition comprising the antibody of claim 12 and a pharmaceutically acceptable carrier or excipient.
17. An isolated antibody that specifically binds to human TIM-3, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 28; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 46.
18. The isolated antibody of claim 17 , wherein the amino acid sequence of the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 28; and the amino acid sequence of the light chain variable region consists of the amino acid sequence of SEQ ID NO: 46.
19. The isolated antibody of claim 17 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 61.
20. The isolated antibody of claim 19 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 61.
21. The isolated antibody of claim 17 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 69.
22. The isolated antibody of claim 21 , wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 69.
23. A pharmaceutical composition comprising the antibody of claim 17 and a pharmaceutically acceptable carrier or excipient.
24. A pharmaceutical composition comprising the antibody of claim 18 and a pharmaceutically acceptable carrier or excipient.
25. A pharmaceutical composition comprising the antibody of claim 19 and a pharmaceutically acceptable carrier or excipient.
26. A pharmaceutical composition comprising the antibody of claim 20 and a pharmaceutically acceptable carrier or excipient.
27. A pharmaceutical composition comprising the antibody of claim 21 and a pharmaceutically acceptable carrier or excipient.
28. A pharmaceutical composition comprising the antibody of claim 22 and a pharmaceutically acceptable carrier or excipient.
29. An isolated antibody that specifically binds to human TIM-3, comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 61; and the light chain comprises the amino acid sequence of SEQ ID NO: 69.
30. The isolated antibody of claim 29 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 61.
31. The isolated antibody of claim 29 , wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 69.
32. The isolated antibody of claim 29 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 61, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 69.
33. A pharmaceutical composition comprising the antibody of claim 29 and a pharmaceutically acceptable carrier or excipient.
34. A pharmaceutical composition comprising the antibody of claim 30 and a pharmaceutically acceptable carrier or excipient.
35. A pharmaceutical composition comprising the antibody of claim 31 and a pharmaceutically acceptable carrier or excipient.
36. A pharmaceutical composition comprising the antibody of claim 32 and a pharmaceutically acceptable carrier or excipient.