Method For Inducing Antitumor Immunity Using Sindbis Viral Vectors And Tumor Associated Antigens

Abstract

The subject application is directed to a method for treating a mammal harboring a tumor comprising identifying a tumor associated antigen (TAA) expressed by the tumor and parenterally administering to the mammal a therapeutically effective amount of a Sindbis viral vector carrying a gene encoding the TAA to the mammal sufficient to elicit an immune response directed against the tumor, and thereby treating the tumor.

1 .- 22 . (canceled) 
     
     
         23 . An immunogenic composition formulated for parenteral delivery, comprising a Sindbis viral vector containing a polynucleotide encoding NY-ESO-1, wherein the Sindbis viral vector is present in an amount sufficient to elicit an anti-tumor immune response in a lymph node and to cause epitope spreading when administered to a subject; and wherein the Sindbis viral vector does not directly target a tumor cell of the subject. 
     
     
         24 . The immunogenic composition of  claim 23 , wherein the elicited anti-tumor immune response is a CD8+ T cell mediated immune response directed against the cells of the tumor. 
     
     
         25 . The immunogenic composition of  claim 23 , wherein the Sindbis viral vector infects the lymph nodes and the infection is followed by induction of T cell activation. 
     
     
         26 . The immunogenic composition of  claim 23 , wherein the Sindbis viral vector is replication defective. 
     
     
         27 . The immunogenic composition of  claim 23 , wherein the Sindbis viral vector is replication competent. 
     
     
         28 . The immunogenic composition of  claim 23 , wherein the subject is a human. 
     
     
         29 . The immunogenic composition of  claim 23 , wherein the tumor is a solid tumor. 
     
     
         30 . The immunogenic composition of  claim 23 , which is a dual expression Sindbis viral vector containing the polynucleotide encoding NY-ESO-1 and a polynucleotide encoding an immune stimulating cytokine selected from interleukin-12 (IL-12) or CCL17. 
     
     
         31 . The immunogenic composition of  claim 23 , which further comprises a polynucleotide encoding a cytokine selected from the group consisting of interleukin-1 (IL-1) through interleukin-36 (IL-36), chemokine (C-C motif) ligand 1 (CCL1) through chemokine (C-C motif) ligand 27 (CCL27), chemokine (C-X-C motif) ligand 1 (CXCLI) through chemokine (C-X-C motif) ligand 13 (CXCL13), and chemokine (C-X3-C motif) (CX3C). 
     
     
         32 . The immunogenic composition of  claim 29 , wherein the solid tumor is an ovarian tumor. 
     
     
         33 . The immunogenic composition of  claim 23 , wherein the parenteral delivery is selected from intraperitoneal, intravenous, or subcutaneous delivery. 
     
     
         34 . The immunogenic composition of  claim 23 , further comprising a pharmaceutically acceptable excipient, vehicle, or diluent. 
     
     
         35 . A method of inducing an anti-tumor immune response in a subject, the method comprising administering to the subject an effective amount of the immunogenic composition of  claim 34 . 
     
     
         36 . The method of  claim 35 , wherein the method treats the tumor. 
     
     
         37 . The method of  claim 35 , wherein the tumor is a NY-ESO-1-expressing tumor. 
     
     
         38 . The method of  claim 37 , wherein the tumor is an ovarian tumor.