Use of mTOR Inhibitors to Enhance T Cell Immune Responses

Abstract

It is disclosed herein that treatment of a subject with an mTOR inhibitor enhances antigen-specific T cell immune responses. Thus, provided herein is a method of enhancing an antigen-specific T cell response in a subject by administering to the subject a therapeutically effective amount of an mTOR inhibitor. The antigen can be any antigen, such as an antigen from a pathogen or a vaccine, or a tumor antigen. In some embodiments, the method further comprises administering to the subject a vaccine, such as a virus vaccine or a cancer vaccine. The mTOR inhibitor can be administered either before or after vaccination to enhance the quantity and quality of the T cell immune response and immunological memory. In some examples, the mTOR inhibitor is rapamycin or a rapamycin analog.

1 . A method of treating cancer comprising administering an effective amount of a composition comprising an mTOR inhibitor in combination with a purified antigen or a vaccine. 
     
     
         2 . The method of  claim 1 , wherein the purified antigen is a tumor antigen. 
     
     
         3 . The method of  claim 2 , wherein the tumor is a hematologic cancer or a solid tumor. 
     
     
         4 . The method of  claim 3 , wherein the hematologic cancer is a leukemia or a lymphoma. 
     
     
         5 . The method of  claim 3 , wherein the solid tumor is a carcinoma, melanoma, sarcoma or central nervous system tumor. 
     
     
         6 . The method of  claim 1 , wherein the tumor antigen is selected from fibroblast growth factor 5, tyrosinase, epithelial tumor antigen (ETA), carcinoembryonic antigen (CEA), beta-human chorionic gonadotropin, alphafetoprotein (AFP), human telomerase reverse transcriptase, thyroglobulin, intestinal carboxyl esterase, macrophage colony stimulating factor, prostase, prostate-specific antigen (PSA), human epidermal growth factor receptor 2, survivin, telomerase, prostate-carcinoma tumor antigen-I, neutrophil elastase, insulin growth factor (IGF)-I, IGF-II, IGF-I receptor, and mesothelin, 
     
     
         7 . The method of  claim 1 , wherein the mTOR inhibitor is rapamycin or analogs.