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 . A method of treating a mammal having a tumor, the method comprising administering by intravenous or intraperitoneal injection to a site of the mammal harboring said tumor an effective amount of a replication defective Sindbis viral vector comprising a gene encoding New York-ESO-1 (NY-ESO-1),
 wherein the Sindbis viral vector does not infect the tumor directly, and   wherein the tumor is treated by NY-ESO-1 specific T cell response in the lymph nodes that drain the site of administration of the Sindbis viral vector.   
     
     
         24 . The method of  claim 23 , wherein the NY-ESO-1 specific T cell response in the lymph nodes is followed by generation and influx of effector and memory NY-ESO-1 specific CD8+ T cells in the tumor, and wherein effector and memory NY-ESO-1 specific CD8+ T cells display cytotoxicity against the NY-ESO-1 positive and negative tumor cells. 
     
     
         25 . The method of  claim 23 , wherein the said Sindbis viral vector introduces the NY-ESO-1 into the lymph nodes prior to activation of a NY-ESO-1 specific immune response by antigen presenting cells (APCs) in the mammal. 
     
     
         26 . The method of  claim 23 , wherein the immune response induced in the lymph nodes of the subject further induces an adaptive anti-tumor immune response comprising activation of NY-ESO-1-specific CD4+ T cells, NK cells, macrophages, monocytes, dendritic cells and neutrophils in the mammal. 
     
     
         27 . The method of  claim 23 , wherein the subject is human. 
     
     
         28 . The method of  claim 23 , wherein the tumor is selected from the group consisting of subcutaneous, intraperitoneal, and lung cancer tumor. 
     
     
         29 . The method of  claim 23 , wherein the tumor is a solid tumor. 
     
     
         30 . The method of  claim 23 , wherein the solid tumor is ovarian cancer tumor. 
     
     
         31 . The method of  claim 23 , wherein the Sindbis viral vector is administered in combination with chemotherapy.