Anti-LAG-3 antibodies and methods of use thereof
The instant disclosure provides antibodies that specifically bind to LAG-3 (e.g., human LAG-3) and antagonize LAG-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 LAG-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: 79, 90, and 98, respectively; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 73.
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: 73.
3. The isolated antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 187.
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: 187.
5. An isolated antibody that specifically binds to human LAG-3, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 65; 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: 100, 104, and 105, respectively.
6. The isolated antibody of claim 5 , wherein the amino acid sequence of the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 65.
7. The isolated antibody of claim 5 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 169.
8. The isolated antibody of claim 7 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 169.
9. An isolated antibody that specifically binds to human LAG-3, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 65; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 73.
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: 65; and the amino acid sequence of the light chain variable region consists of the amino acid sequence of SEQ ID NO: 73.
11. The isolated antibody of claim 9 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 169.
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: 169.
13. The isolated antibody of claim 9 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 187.
14. The isolated antibody of claim 13 , wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 187.
15. An isolated antibody that specifically binds to human LAG-3, comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 169; and the light chain comprises the amino acid sequence of SEQ ID NO: 187.
16. The isolated antibody of claim 15 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 169.
17. The isolated antibody of claim 15 , wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 187.
18. The isolated antibody of claim 15 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 169, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 187.
19. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier or excipient.
20. A pharmaceutical composition comprising the antibody of claim 2 and a pharmaceutically acceptable carrier or excipient.
21. A pharmaceutical composition comprising the antibody of claim 3 and a pharmaceutically acceptable carrier or excipient.
22. A pharmaceutical composition comprising the antibody of claim 4 and a pharmaceutically acceptable carrier or excipient.
23. A pharmaceutical composition comprising the antibody of claim 5 and a pharmaceutically acceptable carrier or excipient.
24. A pharmaceutical composition comprising the antibody of claim 6 and a pharmaceutically acceptable carrier or excipient.
25. A pharmaceutical composition comprising the antibody of claim 7 and a pharmaceutically acceptable carrier or excipient.
26. A pharmaceutical composition comprising the antibody of claim 8 and a pharmaceutically acceptable carrier or excipient.
27. A pharmaceutical composition comprising the antibody of claim 9 and a pharmaceutically acceptable carrier or excipient.
28. A pharmaceutical composition comprising the antibody of claim 10 and a pharmaceutically acceptable carrier or excipient.
29. A pharmaceutical composition comprising the antibody of claim 15 and a pharmaceutically acceptable carrier or excipient.
30. A pharmaceutical composition comprising the antibody of claim 18 and a pharmaceutically acceptable carrier or excipient.
31. A pharmaceutical composition comprising the antibody of claim 11 and a pharmaceutically acceptable carrier or excipient.
32. A pharmaceutical composition comprising the antibody of claim 12 and a pharmaceutically acceptable carrier or excipient.
33. A pharmaceutical composition comprising the antibody of claim 13 and a pharmaceutically acceptable carrier or excipient.
34. A pharmaceutical composition comprising the antibody of claim 14 and a pharmaceutically acceptable carrier or excipient.
35. A pharmaceutical composition comprising the antibody of claim 16 and a pharmaceutically acceptable carrier or excipient.
36. A pharmaceutical composition comprising the antibody of claim 17 and a pharmaceutically acceptable carrier or excipient.