Anticancer agent comprising anti-pd-1 antibody or anti-pd-l1 antibody

Abstract

Provided is an anticancer agent which comprises an anti-PD-1 antibody or an anti-PD-L1 antibody as an active ingredient, functioning to reverse the unresponsiveness of iNKT cells in which anergy has been induced by administration with an iNKT cell ligand. The anti-PD-1 or anti-PD-L1 antibody blocks the PD-1/PD-L1-mediated signaling pathway not only to prevent the iNKT cell ligand-induced iNKT cell anergy, but also to reverse the unresponsiveness of already anergic iNKT cells to produce cytokines. In addition, the anti-PD1 or anti-PD-L1 antibody ensures the potent anti-tumor activity of iNKT cells as demonstrated by a significant reduction in the number of metastatic nodules in B16F10 melanoma metastasis models in vivo. Collectively, the anticancer agent can be very useful in the treatment of cancer, particularly metastatic cancer.

1 . An anticancer agent, comprising an iNKT cell ligand as a first anticancer factor and an anti-PD-1 antibody or anti-PD-L1 antibody as a second anticancer factor, having a function of reversing unresponsiveness of iNKT cells in which anergy is induced by administration with the iNKT cell ligand. 
   
   
       2 . The anticancer agent as defined in  claim 1 , wherein the iNKT cell ligand is selected from a group consisting of alpha-galactosyl ceramide, alpha-glucuronosyl ceramide, phosphatidylinositoltetramannoside, isoglobotrihexosylceramide, ganglioside GD3, phsphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sulfatide, beta-galactosylceramide, lipophosphoglycan, glycoinositol phospholipid, alpha-galactosylceramide analogs including beta-anomer galactoceramide and alpha-anomer galactosylceramide, and bacterial lipid antigens. 
   
   
       3 . The anticancer agent as defined in  claim 1 , wherein the anti-PD-1 antibody or the anti-PD-L1 antibody is a monoclonal antibody or a polyclonal antibody. 
   
   
       4 . The anticancer agent as defined in  claim 1 , wherein the cancer is selected from a group consisting of lung cancer, stomach cancer, liver cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, melanoma, uterine cancer, ovarian cancer, rectal cancer, colorectal cancer, colon cancer, breast cancer, uterine sarcoma, Fallopian tube carcinoma, endometrial carcinoma, uterine cervical carcinoma, vaginal carcinoma, vulva carcinoma, esophageal cancer, larynx cancer, small intestine cancer, thyroid cancer, parathyroid cancer, soft tissue sarcoma, uterine cancer, penis cancer, prostate cancer, chronic or acute leukemia, pediatric solid tumor, differentiated lymphoma, bladder cancer, kidney cancer, renal cell carcinoma, renal pelvic carcinoma, primary CNS lymphoma, spinal cord tumor, brainstem glioma, and pituitary adenoma. 
   
   
       5 . A method for reversing the unresponsiveness of iNKT cells with anergy induced therein by iNKT cell ligand treatment, comprising treating the anergic iNKT cells with an anti-PD-1 antibody or an anti-PD-L1 antibody. 
   
   
       6 . The method as defined in  claim 5 , wherein the iNKT cell ligand is selected from a group consisting of alpha-galactosyl ceramide, alpha-glucuronosyl ceramide, phosphatidylinositoltetramannoside, isoglobotrihexosylceramide, ganglioside GD3, phsphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sulfatide, beta-galactosylceramide, lipophosphoglycan, glycoinositol phospholipid, alpha-galactosylceramide analogs including beta-anomer galactoceramide and alpha-anomer galactosylceramide, and bacterial lipid antigens. 
   
   
       7 . The method as defined in  claim 5 , wherein the anti-PD-1 antibody or the anti-PD-L1 antibody is a monoclonal antibody or a polyclonal antibody.