Cancer immunotherapy by disrupting PD-1/PD-L1 signaling
The disclosure provides a method for immunotherapy of a subject afflicted with cancer, comprises administering to the subject a composition comprising a therapeutically effective amount of an antibody that inhibits signaling from the PD-1/PD-L1 signaling pathway. This disclosure also provides a method for immunotherapy of a subject afflicted with cancer comprising selecting a subject that is a suitable candidate for immunotherapy based on an assessment that the proportion of cells in a test tissue sample from the subject that express PD-L1 on the cell surface exceeds a predetermined threshold level, and administering a therapeutically effective amount of an anti-PD-1 antibody to the selected subject. The invention additionally provides rabbit mAbs that bind specifically to a cell surface-expressed PD-L1 antigen in a FFPE tissue sample, and an automated IHC method for assessing cell surface expression in FFPE tissues using the provided anti-PD-L1 Abs.
1. A method of treating a tumor in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-PD-L1 antibody; wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion; wherein the tumor is derived from a cancer of the renal pelvis; and wherein the tumor is refractory to a platinum based chemotherapy.
2. The method of claim 1 , wherein the tumor is advanced.
3. The method of claim 1 , wherein the tumor is locally advanced.
4. The method of claim 1 , wherein the tumor is metastatic.
5. The method of claim 1 , wherein the therapeutically effective amount of the anti-PD-L1 antibody is administered once every 3 weeks.
6. The method of claim 1 , wherein the anti-PD-L1 antibody is formulated in a pharmaceutical composition.
7. The method of claim 6 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable salt, an anti-oxidant, an aqueous carrier, a non-aqueous carrier, or any combination thereof.
8. The method of claim 7 , wherein the salt comprises a sodium salt.
9. The method of claim 7 , wherein the salt comprises sodium chloride.
10. The method of claim 1 , wherein at least 1% of tumor cells exhibit membrane PD-L1 expression.
11. The method of claim 1 , wherein at least 5% of tumor cells exhibit membrane PD-L1 expression.
12. The method of claim 1 , further comprising administering an anti-cancer agent.
13. The method of claim 2 , further comprising administering an anti-cancer agent.
14. The method of claim 3 , further comprising administering an anti-cancer agent.
15. The method of claim 4 , further comprising administering an anti-cancer agent.
16. The method of claim 10 , further comprising administering an anti-cancer agent.
17. The method of claim 12 , wherein the anti-cancer agent is a chemotherapy.
18. The method of claim 12 , wherein the anti-cancer agent is a radiotherapy.
19. The method of claim 13 , wherein the anti-cancer agent is a chemotherapy.
20. The method of claim 13 , wherein the anti-cancer agent is a radiotherapy.
21. The method of claim 14 , wherein the anti-cancer agent is a chemotherapy.
22. The method of claim 14 , wherein the anti-cancer agent is a radiotherapy.
23. The method of claim 1 , wherein the platinum-based chemotherapy comprises cisplatin, carboplatin, or both.
24. The method of claim 1 , wherein the subject is further administered a corticosteroid.
25. A method of treating a tumor in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-PD-L1 antibody once every 3 weeks;
wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion;
wherein the tumor is derived from a cancer of the renal pelvis;
wherein the tumor is advanced or metastatic; and
wherein the tumor is refractory to a platinum based chemotherapy.
26. The method of claim 1 , wherein the subject is administered an antihistamine prior to the anti-PD-L1 antibody.
27. The method of claim 25 , wherein the subject is administered an antihistamine prior to the anti-PD-L1 antibody.
28. A method of treating a tumor in a human subject in need thereof, comprising administering to the subject about 10 mg/kg of an anti-PD-L1 antibody once every 2 weeks, wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion; wherein the tumor is derived from a cancer of the renal pelvis; and wherein the tumor is refractory to a platinum based chemotherapy.
29. The method of claim 28 , wherein the tumor is locally advanced or metastatic.
30. The method of claim 28 , wherein at least 1% of tumor cells exhibit membrane PD-L1 expression.