Immunopotentiative Composition

Abstract

Compositions for cancer or infection treatment via immunopotentiation caused by inhibition of immunosuppressive signal induced by PD-1, PD-L1, or PD-L2 and therapies using them, immunopotentiative substrates included as the active ingredient, screening methods of the substrates for cancer or infection treatment, cell lines used for the screening methods, evaluation methods that selects the substrates for cancer treatment, and carcinoma cell transplanted mammals used for the evaluation methods. The compositions of the present invention that inhibits the function of PD-1, PD-L1, or PD-L2 are useful for cancer or infection treatment.

1 . (canceled) 
     
     
         2 . A method of treating a tumor in a subject in need thereof comprising administering to the subject an immunosuppressive signal inhibitor of PD-1, PD-L1, or PD-L2. 
     
     
         3 . The method of  claim 2 , wherein the immunosuppressive signal inhibitor suppresses cancer metastasis. 
     
     
         4 . A method of treating an infection in a subject in need thereof comprising administering to the subject an immunosuppressive signal inhibitor of PD-1, PD-L1 or PD-L2. 
     
     
         5 . The method of  claim 2 , wherein the immunosuppressive signal inhibitor acts through immunopotentiation. 
     
     
         6 . The method of  claim 4 , wherein the immunosuppressive signal inhibitor acts through immunopotentiation. 
     
     
         7 . The method of  claim 2 , wherein the immunosuppressive signal inhibitor is one or more selected from an interaction inhibitor of PD-1 and PD-L1 or PD-1 and PD-L2, an intracellular signaling inhibitor of PD-1, and a production inhibitor of PD-1, PD-L1 or PD-L2. 
     
     
         8 . The method of  claim 7 , wherein the interaction inhibitor of PD-1 and PD-L1 is one or more selected from an anti-PD-1 antibody, an anti-PD-L1 antibody, soluble PD-1, and soluble PD-L1. 
     
     
         9 . The method of  claim 8 , wherein the anti-PD-1 antibody is selected from an anti-human PD-1 antibody produced by a hybridoma internationally deposited as FERM BP-8392, a humanized anti-human PD-1 antibody, and a human anti-human PD-1 antibody. 
     
     
         10 . The method of  claim 2 , wherein the immunosuppressive signal inhibitor is a lymphocyte in which PD-1 expression is inhibited by gene-recombination. 
     
     
         11 . The method of  claim 7 , wherein the interaction inhibitor of PD-1 and PD-L1 or PD-1 and PD-L2, the intracellular signaling inhibitor of PD-1, or the production inhibitor of PD-1, PD-L1 or PD-L2 is one or more substances selected from a protein, a polypeptide, a peptide, a polynucleotide, a polynucleoside, an antibody or a derivative thereof, an organic synthesis compound, an inorganic compound, and a natural product. 
     
     
         12 - 28 . (canceled) 
     
     
         29 . A method of screening for a substance for treatment of cancer, comprising contacting a test substance with a carcinoma cell expressing PD-L1 or PD-L2 and a lymphocyte, wherein the test substance enhances an immune reaction of the lymphocyte to the carcinoma cell and thereby inhibits carcinoma cell proliferation. 
     
     
         30 . A method of screening for a substance for treatment of infection, comprising contacting a test substance with a cell, which expresses PD-L1 or PD-L2 and is infected with a pathogen, and a lymphocyte, wherein the test substance enhances immune reaction of the lymphocyte to the infected cell and thereby inhibits pathogen proliferation. 
     
     
         31 - 32 . (canceled) 
     
     
         33 . The method of  claim 2 , wherein the tumor comprises squamous carcinoma. 
     
     
         34 . The method of  claim 33 , wherein the squamous carcinoma comprises a tumor in a tissue selected from cervical canal, eyelid, tunica conjunctiva, vagina, lung, oral cavity, skin, urinary bladder, tongue, larynx, and gullet. 
     
     
         35 . The method of  claim 2 , wherein the tumor comprises adenocarcinoma. 
     
     
         36 . The method of  claim 35 , wherein the adenocarcinoma comprises a tumor in a tissue selected from prostate, small intestine, endometrium, cervical canal, large intestine, lung, pancreas, gullet, intestinum rectum, uterus, stomach, mammary gland, and ovary. 
     
     
         37 . The method of  claim 2 , wherein the tumor comprises sarcomata. 
     
     
         38 . The method of  claim 37 , wherein the sarcomata comprises a tumor in a tissue selected from myogenic sarcoma, leukosis, neuroma, melanoma, and lymphoma. 
     
     
         39 . The method of  claim 2 , wherein the tumor expresses PD-L1. 
     
     
         40 . The method of  claim 2 , wherein the tumor expresses PD-L2.