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 skin cancer in a human subject in need thereof, comprising administering to the subject about 10 mg/kg of an anti-PD-L1 antibody every 2 weeks, wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion, wherein the subject is administered an antihistamine and an antipyretic prior to the anti-PD-L1 antibody, and wherein at least 1% of tumor cells of the skin cancer exhibit membrane PD-L1 expression.
2. The method of claim 1 , wherein the skin cancer is metastatic.
3. The method of claim 1 , wherein the skin cancer is advanced.
4. The method of claim 3 , wherein the skin cancer is locally advanced.
5. The method of claim 1 , wherein the skin cancer is refractory to a standard-of-care therapy for treating the skin cancer.
6. The method of claim 1 , wherein the anti-PD-L1 antibody is administered every 2 weeks for more than 12 weeks.
7. The method of claim 1 , wherein the anti-PD-L1 antibody is formulated in a pharmaceutical composition.
8. The method of claim 7 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable salt, an anti-oxidant, an aqueous carrier, a non-aqueous carrier, or any combination thereof.
9. The method of claim 8 , wherein the pharmaceutical composition comprises a preservative, a wetting agent, an emulsifying agent, a dispersing agent, or any combination thereof.
10. The method of claim 8 , wherein the salt comprises a sodium salt.
11. The method of claim 8 , wherein the salt comprises sodium chloride.
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 5 , further comprising administering an anti-cancer agent.
17. The method of claim 6 , further comprising administering an anti-cancer agent.
18. The method of claim 12 , wherein the anti-cancer agent is a chemotherapy.
19. The method of claim 13 , wherein the anti-cancer agent is a chemotherapy.
20. The method of claim 14 , wherein the anti-cancer agent is a chemotherapy.
21. The method of claim 15 , wherein the anti-cancer agent is a chemotherapy.
22. The method of claim 16 , wherein the anti-cancer agent is a chemotherapy.
23. The method of claim 17 , wherein the anti-cancer agent is a chemotherapy.
24. The method of claim 1 , wherein the subject has been previously treated with an anti-cancer therapy.
25. A method of treating a skin cancer in a human subject in need thereof, comprising administering an antihistamine and an antipyretic prior to an anti-PD-L1 antibody and administering to the subject about 10 mg/kg of the anti-PD-L1 antibody every 2 weeks, wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion, and wherein at least 1% of tumor cells of the skin cancer exhibit membrane PD-L1 expression.
26. A method of treating a metastatic skin cancer in a human subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising an anti-PD-L1 antibody and a sodium salt, wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion, wherein the subject is administered an antihistamine and an antipyretic prior to the anti-PD-L1 antibody, and wherein at least 1% of tumor cells of the skin cancer exhibit membrane PD-L1 expression.
27. The method of claim 26 , wherein the sodium salt is sodium chloride.