Antibodies to PD-1 and uses thereof
Provided herein are various embodiments relating to antibodies. Some of the embodiments include antagonist antibodies that bind PD-1. Such antibodies can be used in methods to treat, for example, cancer.
1. An isolated monoclonal antibody that binds to human Programmed Death 1 (PD-1), wherein the antibody comprises (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 21; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 22; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 23; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 25; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 26; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 27.
2. The isolated monoclonal antibody of claim 1 , wherein the antibody comprises a heavy chain variable region (V H ) that is at least 90% identical to the amino acid sequence of SEQ ID NO: 20 and a light chain variable region (V L ) that is at least 90% identical to the amino acid sequence of SEQ ID NO: 24.
3. The isolated monoclonal antibody of claim 1 , comprising a V H comprising the amino acid sequence of SEQ ID NO: 20 and a V L comprising the amino acid sequence of SEQ ID NO: 24.
4. The isolated monoclonal antibody of claim 1 , wherein the antibody binds to human PD-1 with an affinity (K D ) of less than 5 nM.
5. The isolated monoclonal antibody of claim 4 , wherein the antibody binds to mouse PD-1 with an affinity (K D ) of less than 10 nM.
6. The isolated monoclonal antibody of claim 4 , wherein affinity is determined using biolayer interferometry.
7. The isolated monoclonal antibody of claim 1 , wherein the antibody is a human antibody or a chimeric antibody.
8. The isolated monoclonal antibody of claim 1 , wherein the antibody is an antibody fragment selected from a Fab, Fab′, Fv, scFv or (Fab′) 2 fragment.
9. The isolated monoclonal antibody of claim 1 , wherein the antibody is a full length antibody.
10. The isolated monoclonal antibody of claim 1 , wherein the antibody binds cynomolgus monkey PD-1.
11. The isolated monoclonal antibody of claim 1 , wherein the antibody inhibits binding of human PD-1 to human PD-L1 and inhibits the binding of human PD-1 to human PD-L2.
12. The isolated monoclonal antibody of claim 1 , wherein administration of the antibody to a mammal increases the level of at least one cytokine selected from IFNγ and IL-2.
13. The isolated monoclonal antibody of claim 12 , wherein the antibody increases the level of at least one cytokine selected from IFNγ and IL-2 by at least 2-fold.
14. The isolated monoclonal antibody of claim 13 , wherein the level of the cytokine is measured 24 hours after administration of the antibody.
15. The isolated monoclonal antibody of claim 1 , wherein administration of the antibody to a mammal enhances an immune response in the mammal.
16. The isolated monoclonal antibody of claim 1 , wherein administration of the antibody to a mammal results in activation of T cells in the mammal.
17. The isolated monoclonal antibody of claim 1 , wherein administration of the antibody to a mammal reduces tumor size in a mammal with cancer.
18. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
19. The isolated monoclonal antibody of claim 2 , wherein the antibody is a human antibody.
20. The isolated monoclonal antibody of claim 3 , wherein the antibody is a human antibody.
21. The isolated monoclonal antibody of claim 1 , wherein the antibody comprises a human IgG4 constant region.
22. The isolated monoclonal antibody of claim 2 , wherein the antibody comprises a human IgG4 constant region.
23. The isolated monoclonal antibody of claim 3 , wherein the antibody comprises a human IgG4 constant region.
24. The isolated monoclonal antibody of claim 2 , wherein the antibody binds to human PD-1 with an affinity (K D ) of less than 5 nM.
25. The isolated monoclonal antibody of claim 24 , wherein affinity is determined using biolayer interferometry.
26. The isolated monoclonal antibody of claim 3 , wherein the antibody binds to human PD-1 with an affinity (K D ) of less than 5 nM.
27. The isolated monoclonal antibody of claim 26 , wherein affinity is determined using biolayer interferometry.
28. The isolated monoclonal antibody of claim 2 , wherein the antibody binds cynomolgus monkey PD-1.
29. The isolated monoclonal antibody of claim 3 , wherein the antibody binds cynomolgus monkey PD-1.
30. The isolated monoclonal antibody of claim 2 , wherein the antibody inhibits binding of human PD-1 to human PD-L1 and inhibits the binding of human PD-1 to human PD-L2.
31. The isolated monoclonal antibody of claim 3 , wherein the antibody inhibits binding of human PD-1 to human PD-L1 and inhibits the binding of human PD-1 to human PD-L2.
32. A pharmaceutical composition comprising the antibody of claim 2 and a pharmaceutically acceptable carrier.
33. A pharmaceutical composition comprising the antibody of claim 3 and a pharmaceutically acceptable carrier.
34. A pharmaceutical composition comprising the antibody of claim 21 and a pharmaceutically acceptable carrier.
35. A pharmaceutical composition comprising the antibody of claim 22 and a pharmaceutically acceptable carrier.
36. A pharmaceutical composition comprising the antibody of claim 23 and a pharmaceutically acceptable carrier.