Anti-PD-1 antibodies
Antibodies that bind to programmed cell death protein 1 (PD-1), compositions comprising such antibodies, and methods of making and using such antibodies are disclosed.
1. An isolated antibody that binds to programmed cell death protein 1 (PD-1), comprising a heavy chain variable region (HCVR) having complementarity determining regions (CDRs) 1-3 of SEQ ID NO: 20, and a light chain variable region (LCVR) having CDRs 1-3 of SEQ ID NO: 53.
2. The antibody according to claim 1 , wherein the antibody comprises a HCVR having the sequence set forth in SEQ ID NO: 20 and a LCVR having the sequence set forth in SEQ ID NO: 53 (246A10).
3. The antibody according to claim 1 comprising a humanized or human framework region.
4. The antibody according to claim 1 , wherein the antibody binds to a sequence in PD-1 selected from the group consisting of SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 82, SEQ ID NO: 83, and SEQ ID NO: 84.
5. The antibody according to claim 1 , wherein the antibody is monoclonal.
6. The antibody according to claim 1 , wherein the antibody is a PD-1 agonist.
7. The antibody according to claim 1 , wherein the antibody is a PD-1 antagonist.
8. An isolated nucleic acid comprising a nucleotide sequence encoding the antibody of claim 1 .
9. An expression vector comprising the nucleic acid of claim 8 .
10. A host cell transformed with an expression vector of claim 9 .
11. A method of producing an antibody comprising a HCVR, a LCVR, or a combination thereof, the method comprising:
a) growing the host cell of claim 10 , under conditions such that the host cell expresses the antibody comprising the HCVR, the LCVR, or a combination thereof; and
b) isolating the antibody comprising the HCVR, the LCVR, or combination thereof.
12. A method of treating cancer in a mammal in need thereof, comprising administering an effective amount of the antibody according to claim 7 to the mammal.
13. A method of diagnosing a PD-1-mediated adaptive immune resistance in a patient who has cancer, comprising:
contacting a tumor microenvironment in the patient with the antibody according to claim 1 labeled with a detectable moiety; and
detecting expression of PD-1 on CD8+ T cells within the tumor microenvironment.
14. The method of claim 13 , further comprising detecting expression of PD-L1 in the tumor microenvironment.
15. A method for increasing T cell effector function, comprising contacting a T cell with the antibody of claim 7 .