Anti-CTLA-4 antibodies and methods of use thereof
The instant disclosure provides antibodies that specifically bind to human CTLA-4 and antagonize CTLA-4 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 CTLA-4 protein, comprising: a heavy chain variable region comprising the CDRH1, CDRH2 and CDRH3 amino acid sequences of SEQ ID NOs: 1, 2, and 3, respectively; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8.
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: 8.
3. The isolated antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 13.
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: 13.
5. An isolated antibody that specifically binds to human CTLA-4 protein, comprising: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7; and a light chain variable region comprising the CDRL1, CDRL2 and CDRL3 amino acid sequences of SEQ ID NOs: 4, 5, and 6, 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: 7.
7. The isolated antibody of claim 5 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 93.
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: 93.
9. The isolated antibody of claim 5 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 12.
10. The isolated antibody of claim 9 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 12.
11. An isolated antibody that specifically binds to human CTLA-4 protein, comprising: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8.
12. The isolated antibody of claim 11 , wherein the amino acid sequence of the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 7, and the amino acid sequence of the light chain variable region consists of the amino acid sequence of SEQ ID NO: 8.
13. An isolated antibody that specifically binds to human CTLA-4 protein, comprising: a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 93; and the light chain comprises the amino acid sequence of SEQ ID NO: 13.
14. The isolated antibody of claim 13 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 93.
15. The isolated antibody of claim 13 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 12.
16. The isolated antibody of claim 13 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 12.
17. 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: 13.
18. The isolated antibody of claim 13 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 93, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 13.
19. The isolated antibody of claim 13 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 12, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 13.
20. The isolated antibody of claim 13 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 12, and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 13.
21. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier or excipient.
22. A pharmaceutical composition comprising the antibody of claim 5 and a pharmaceutically acceptable carrier or excipient.
23. A pharmaceutical composition comprising the antibody of claim 11 and a pharmaceutically acceptable carrier or excipient.
24. A pharmaceutical composition comprising the antibody of claim 12 and a pharmaceutically acceptable carrier or excipient.
25. A pharmaceutical composition comprising the antibody of claim 13 and a pharmaceutically acceptable carrier or excipient.
26. A pharmaceutical composition comprising the antibody of claim 18 and a pharmaceutically acceptable carrier or excipient.
27. A pharmaceutical composition comprising the antibody of claim 20 and a pharmaceutically acceptable carrier or excipient.
28. The isolated antibody of claim 11 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 93.
29. The isolated antibody of claim 28 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 93.
30. The isolated antibody of claim 11 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 12.
31. The isolated antibody of claim 30 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 12.
32. The isolated antibody of claim 11 , wherein the antibody comprises a light chain amino acid sequence of SEQ ID NO: 13.
33. The isolated antibody of claim 32 , wherein the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 13.
34. The isolated antibody of claim 11 , wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 97; and the light chain comprises the amino acid sequence of SEQ ID NO: 13.