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 metastatic non-small cell lung cancer (NSCLC) in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of nivolumab in combination with a platinum-based doublet chemotherapy; wherein the nivolumab is administered by intravenous infusion; and wherein at least 10% of tumor cells of the NSCLC exhibit membrane PD-L1 expression.
2 . The method of claim 1 , wherein the therapeutically effective amount of the nivolumab is administered once every 3 weeks.
3 . The method of claim 1 , wherein the nivolumab is formulated in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
4 . The method of claim 3 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable salt, an adjuvant, an anti-oxidant, or any combination thereof.
5 . The method of claim 4 , wherein the salt comprises a sodium salt.
6 . The method of claim 4 , wherein the salt comprises sodium chloride.
7 . The method of claim 1 , wherein the NSCLC is resectable.
8 . The method of claim 7 , wherein the nivolumab is further combined with a surgery to treat the NSCLC.
9 . The method of claim 1 , wherein the membranous PD-L1 expression on the tumor cells is measured prior to the administering of the nivolumab.
10 . The method of claim 9 , wherein the measuring comprises an immunohistochemistry.
11 . The method of claim 10 , wherein the immunohistochemistry is performed using an antibody comprising (a) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 35, and (b) a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 36.
12 . The method of claim 1 , wherein the platinum-based doublet chemotherapy comprises cisplatin, carboplatin, paclitaxel, albumin-bound paclitaxel, docetaxel, vinorelbine, vinblastine, etoposide, pemetrexed, gemcitabine, or a combination thereof.
13 . The method of claim 1 , wherein the platinum-based doublet chemotherapy comprises cisplatin or carboplatin.
14 . The method of claim 13 , wherein the platinum-based doublet chemotherapy comprises paclitaxel, albumin-bound paclitaxel, docetaxel, vinorelbine, vinblastine, etoposide, pemetrexed, or gemcitabine.
15 . A method of treating a resectable metastatic non-small cell lung cancer (NSCLC) in a human subject in need thereof, comprising:
(i) a surgery, in combination with
(ii) administering to the subject once every three weeks a therapeutically effective amount of nivolumab in combination with a platinum-based doublet chemotherapy;
wherein the nivolumab is administered by intravenous infusion;
wherein the platinum-based doublet chemotherapy comprises (i) cisplatin or carboplatin and (ii) paclitaxel, albumin-bound paclitaxel, docetaxel, vinorelbine, vinblastine, etoposide, pemetrexed, or gemcitabine; and
wherein at least 10% of tumor cells of the NSCLC exhibit membrane PD-L1 expression.
16 . The method of claim 15 , wherein the surgery is performed prior to the administering of the nivolumab.
17 . The method of claim 15 , wherein the nivolumab is formulated in a pharmaceutical composition comprising a pharmaceutically acceptable carrier, a pharmaceutically acceptable salt, an adjuvant, an anti-oxidant, or any combination thereof.
18 . The method of claim 15 , wherein the membranous PD-L1 expression on the tumor cells is measured prior to the administering of the nivolumab.
19 . The method of claim 18 , wherein the measuring comprises an immunohistochemistry.
20 . The method of claim 19 , wherein the immunohistochemistry is performed using an antibody comprising (a) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 35, and (b) a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 36.