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 cancer of the head or neck in a human subject in need thereof, comprising administering to the subject an anti-PD-L1 antibody once every 3 weeks, wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion, wherein at least 1% of tumor cells of the cancer exhibit membrane PD-L1 expression, and wherein the subject is administered an antihistamine and an antipyretic prior to the anti-PD-L1 antibody.
2. The method of claim 1 , wherein the cancer of the head or neck is a squamous cell carcinoma of the head or neck.
3. The method of claim 1 , further comprising administering a standard of care chemotherapeutic regimen.
4. The method of claim 2 , wherein the standard of care chemotherapeutic regimen is administered prior to the anti-PD-L1 antibody.
5. The method of claim 2 , wherein the standard of care chemotherapeutic regimen comprises a platinum-based chemotherapy.
6. The method of claim 4 , wherein the platinum-based chemotherapy comprises cisplatin.
7. The method of claim 1 , further comprising administering a radiation therapy.
8. The method of claim 2 , further comprising administering cisplatin and a radiation therapy.
9. The method of claim 7 , wherein the cisplatin is administered prior to the anti-PD-L1 antibody.
10. A method of treating a cancer of the head or neck in a human subject in need thereof, comprising administering to the subject (i) a standard of care chemotherapeutic regimen and (ii) an anti-PD-L1 antibody, wherein the anti-PD-L1 antibody is administered once every 3 weeks intravenously over 60 minutes infusion.
11. The method of claim 10 , wherein the cancer of the head or neck is a squamous cell carcinoma of the head or neck.
12. The method of claim 10 , wherein the standard of care chemotherapeutic regimen is administered prior to the anti-PD-L1 antibody.
13. The method of claim 10 , wherein the standard of care chemotherapeutic regimen comprises cisplatin.
14. The method of claim 10 , further comprising administering a radiation therapy.
15. The method of claim 10 , wherein the standard of care chemotherapeutic regimen comprises cisplatin, and wherein the subject is further administered a radiation therapy.
16. The method of claim 15 , wherein the cisplatin and the radiation therapy are administered prior to the anti-PD-L1 antibody.
17. The method of claim 10 , further comprising administering an antihistamine and an antipyretic prior to the anti-PD-L1 antibody.
18. The method of claim 1 , wherein the cancer is advanced.
19. The method of claim 18 , wherein the cancer is locally advanced.
20. The method of claim 10 , wherein the cancer is advanced.
21. The method of claim 20 , wherein the cancer is locally advanced.
22. The method of claim 10 , wherein at least 1% of tumor cells of the cancer exhibit membrane PD-L1 expression.
23. A method of treating squamous cell carcinoma of the head or neck in a human subject in need thereof, comprising administering to the subject (i) a standard of care chemotherapeutic regimen and (ii) an anti-PD-L1 antibody, wherein the anti-PD-L1 antibody is administered once every 3 weeks intravenously, wherein the standard of care chemotherapeutic regimen comprises cisplatin, wherein at least 1% of tumor cells of the cancer exhibit membrane PD-L1 expression, and wherein the subject is administered an antihistamine and an antipyretic prior to the anti-PD-L1 antibody.
24. The method of claim 23 , further comprising administering a radiation therapy.
25. The method of claim 23 , wherein the squamous cell carcinoma of the head or neck is locally advanced.
26. A method of treating squamous cell carcinoma of the head or neck in a human subject in need thereof, comprising administering to the subject a combination of (i) a standard of care chemotherapeutic regimen and (ii) 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 standard of care chemotherapeutic regimen comprises cisplatin, wherein at least 1% of tumor cells of the cancer exhibit membrane PD-L1 expression, and wherein the subject is administered an antihistamine and an antipyretic prior to the anti-PD-L1 antibody.
27. The method of claim 26 , wherein the cancer of the head or neck is a squamous cell carcinoma of the head or neck.