Checkpoint Inhibitor and Vaccine Combinations and Use of Same for Immunotherapy

Abstract

Disclosed herein is a vaccine comprising an antigen and checkpoint inhibitor. Also disclosed herein is a method for enhancing an immune response in a subject. The method may comprise administering the vaccine to the subject in need thereof.

1 . A composition for enhancing an immune response against an antigen in a subject in need thereof, comprising:
 a) TIM-3 antibody or LAG-3 antibody, and   b) a synthetic antigen capable of generating an immune response in the subject, or a biologically functional fragment or variant thereof.   
     
     
         2 . The composition of  claim 1  wherein the synthetic antigen is an isolated DNA that encodes for the antigen. 
     
     
         3 . The composition of  claim 2  wherein the synthetic antigen is selected from the group consisting of: prostate, WT1, tyrosinase, NYES01, PRAME, MAGE, CMV, herpes, HIV, HPV, HCV, HBV, influenza, RSV,  Plasmodium falciparum , and  C. difficle.    
     
     
         4 . The composition of  claim 3 , wherein the HPV antigen is E6 and E7 domains of subtypes selected from the group consisting of: HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV52, and HPV58, and a combination thereof. 
     
     
         5 . The composition of  claim 3 , wherein the HIV antigen is selected from the group consisting of: Env A, Env B, Env C, Env D, B Nef-Rev, and Gag, and a combination thereof. 
     
     
         6 . The composition of  claim 3 , wherein the influenza antigen is selected from the group consisting of: H1 HA, H2 HA, H3 HA, H5 HA, BHA antigen, and any combination thereof. 
     
     
         7 . The composition of  claim 3 , wherein the  Plasmodium falciparum  antigen includes a circumsporozoite (CS) antigen. 
     
     
         8 . The composition of  claim 3 , wherein the  C. difficle  antigen is selected from the group consisting of: Toxin A, and Toxin B, and a combination thereof. 
     
     
         9 . The composition of  claim 3 , wherein the HCV antigen is selected from the group consisting of: E1, E2, NS3, NS4a, NS4b, NS5a, and NS5b, and a combination thereof. 
     
     
         10 . The composition of  claim 3 , wherein the HBV antigen is selected from the group consisting of: surface antigen type A, surface antigen type B, surface antigen type C, surface antigen type D, surface antigen type E, surface antigen type F, surface antigen type G, surface antigen type H, and core antigen, and a combination thereof. 
     
     
         11 . The composition of  claim 3 , wherein the RSV antigen is selected from the group consisting of: F, G, NS1, NS2, N, M, M2-1, M2-2, P, SH, and L protein, and a combination thereof. 
     
     
         12 . (canceled) 
     
     
         13 . The composition of  claim 3 , wherein the prostate antigen is selected from the group consisting of: PSA, PSMA, STEAP, PSCA, and PAP, and a combination thereof. 
     
     
         14 . The composition of  claim 3 , wherein the synthetic antigen is selected from the group consisting of WT1 antigen, tyrosinase, NYES01 and PRAME. 
     
     
         15 .- 17 . (canceled) 
     
     
         18 . The composition of  claim 1 , further comprising a pharmaceutically acceptable excipient. 
     
     
         19 . A method for increasing an immune response in a subject in need thereof, the method comprising administering the composition of  claim 1  to the subject. 
     
     
         20 . The method of  claim 19 , wherein administering the composition comprises an electroporating step. 
     
     
         21 . A method of increasing an immune response in a subject in need thereof by administering a combination of synthetic antigen and checkpoint inhibitor, wherein the administering step comprises:
 administering to the subject a prime vaccination and a boost vaccination of synthetic antigen, and   subsequent to the boost vaccination, administering to the subject a checkpoint inhibitor.   
     
     
         22 . The method of  claim 21 , further comprising a step of further administering to the subject a subsequent boost vaccination of the synthetic antigen. 
     
     
         23 . The method of  claim 22 , wherein any of the administering steps include delivering electroporation to site of administration.