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 an ovarian cancer in a human subject in need thereof, comprising administering to the subject an anti-PD-L1 antibody once every 2 weeks, wherein the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion, wherein at least 1% of tumor cells of the ovarian 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 , further comprising administering a standard of care chemotherapeutic regimen.
3. The method of claim 2 , wherein the standard of care chemotherapeutic regimen is administered prior to the anti-PD-L1 antibody.
4. The method of claim 2 , wherein the standard of care chemotherapeutic regimen comprises a platinum based chemotherapy.
5. The method of claim 4 , wherein the platinum based chemotherapy comprises carboplatin.
6. The method of claim 2 , wherein the standard of care chemotherapeutic regimen comprises paclitaxel.
7. The method of claim 2 , further comprising administering carboplatin and paclitaxel.
8. The method of claim 7 , wherein the carboplatin and paclitaxel are administered prior to the anti-PD-L1 antibody.
9. The method of claim 7 , wherein the carboplatin, the paclitaxel, or both the carboplatin and the paclitaxel are administered on the same day as the anti-PD-L1 antibody.
10. A method of treating an ovarian cancer in a human subject in need thereof, comprising administering to the subject a standard of care chemotherapeutic regimen in combination with an anti-PD-L1 antibody, wherein the anti-PD-L1 antibody is administered once every 3 weeks intravenously over 60 minutes infusion and wherein at least 1% of tumor cells of the ovarian cancer exhibit membrane PD-L1 expression.
11. The method of claim 10 , wherein the standard of care chemotherapeutic regimen is administered prior to the anti-PD-L1 antibody.
12. The method of claim 10 , wherein the standard of care chemotherapeutic regimen comprises carboplatin.
13. The method of claim 10 , wherein the standard of care chemotherapeutic regimen comprises paclitaxel.
14. The method of claim 10 , wherein the standard of care chemotherapeutic regimen comprises carboplatin and paclitaxel.
15. The method of claim 14 , wherein the carboplatin, the paclitaxel, or both the carboplatin and the paclitaxel are administered on the same day as the anti-PD-L1 antibody.
16. The method of claim 15 , wherein the carboplatin is administered on the same day as 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 ovarian cancer is metastatic.
19. The method of claim 1 , wherein the ovarian cancer is advanced.
20. The method of claim 19 , wherein the ovarian cancer is locally advanced.
21. The method of claim 1 , wherein the ovarian cancer is refractory.
22. The method of claim 10 , wherein the ovarian cancer is metastatic.
23. The method of claim 10 , wherein the ovarian cancer is advanced.
24. The method of claim 23 , wherein the ovarian cancer is locally advanced.
25. The method of claim 10 , wherein the anti-PD-L1 antibody is administered at a dose of about 10 mg/kg.
26. A method of treating an ovarian cancer 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 carboplatin and/or paclitaxel, wherein at least 1% of tumor cells of the ovarian 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 sodium salt is sodium chloride.