Stat3 antagonists and their uses as vaccines against cancer

Abstract

The present invention relates to methods for treating and/or preventing cancer. In particular the present invention relates to ex vivo immunotherapeutic methods. The methods comprise decreasing Stat3 (signal transducer and activator of transcirption3) expression and/or function in tumor cells and the administration of such cells to a subject in need of treatment and/or prevention. Other methods of the invention comprise activation T-cells by co-culturing the T-cells with the tumor cells with decreased Stat3 expression or function. The invention further encompasses methods comprising decreasing Stat3 expression or function in antigen-presenting cells and co-administering tumor cells and the antigen-presenting cells with decreased Stat3 function to a patient. The invention further relates to methods for stimulating dendritic cell differentiation.

1 . A method for treating and/or preventing cancer in a subject, wherein the method comprising administering antigen-presenting cells and tumor cells to the subject, thereby stimulating an immune-response in the subject such that the cancer is treated or prevented, wherein said antigen-presenting cells have decreased Stat3 expression or function, and wherein said tumor cells are inactivated to prevent further cell division of said tumor cells. 
     
     
         2 . The method of  claim 1 , wherein at least one of the antigen-presenting cells is a macrophage. 
     
     
         3 . The method of  claim 1 , wherein at least one of the antigen-presenting cells is a dendritic cell. 
     
     
         4 . The method of  claim 1 , wherein decreasing Stat3 expression or function comprises expressing a dominant negative Stat3 gene in the antigen presenting cells. 
     
     
         5 . The method of  claim 1 , wherein decreasing Stat3 expression or function comprises introducing anti-Stat3 antibodies to the antigen presenting cells. 
     
     
         6 . The method of  claim 1 , wherein decreasing Stat3 expression or function comprises introducing Stat3-specific antisense nucleotide sequences to the antigen presenting cells. 
     
     
         7 . The method of  claim 1 , wherein decreasing Stat3 expression or function comprises introducing a mutation in the Stat3 gene of the antigen presenting cells or deleting the Stat3 gene in the antigen presenting cells. 
     
     
         8 . The method of  claim 2 , wherein said macrophages, before administration to said subject, are activated by treating with LPS. 
     
     
         9 . The method of  claim 2 , wherein said macrophages, before administration to said subject, are activated by treating with IFN-gamma. 
     
     
         10 . The method of  claim 2 , wherein said macrophages, before administration to said subject, are activated by treating with 1FN-gamma and LPS. 
     
     
         11 . The method of  claim 1 , wherein the tumor cells have been treated with GM-CSF. 
     
     
         12 . The method of  claim 1 , wherein the method further comprises administering GM-CSF to the subject. 
     
     
         13 . The method of  claim 1 , wherein the subject is human. 
     
     
         14 . A method for treating and/or preventing cancer in a subject, wherein the method comprises: (a) decreasing Stat3 expression or function in antigen-presenting cells; (b) administering the antigen-presenting cells of step (a) and a molecule that displays the antigenicity of a tumor cell of the cancer to the subject, thereby stimulating an immune-response in the subject, such that the cancer is treated or prevented. 
     
     
         15 . A method for treating and/or preventing cancer in a subject, wherein the method comprises: (a) decreasing Stat3 expression or function in antigen-presenting cells; (b) culturing the antigen-presenting cells of step (a) with a molecule that displays the antigenicity of a tumor cell of the cancer to the subject, (c) administering the antigen-presenting cells to the subject in an amount effective to stimulate an immune response in the subject, thereby stimulating an immune response in the subject, such that the cancer is treated or prevented. 
     
     
         16 . A method for treating and/or preventing an infectious disease in a subject, wherein the method comprises: (a) decreasing Stat3 expression or function in antigen-presenting cells; (b) inactivating the agent that causes the infectious disease such that the inactivated agent is incapable of causing disease; and (c) administering the antigen-presenting cells of step (a) and the infectious agent of step (b) to the subject, thereby stimulating an immune-response in the subject, such that the infectious disease is treated or prevented. 
     
     
         17 . A method for treating and/or preventing an infectious disease in a subject, wherein the method comprises: (a) decreasing Stat3 expression or function in antigen-presenting cells; and (b) administering to the subject the antigen presenting cells of step (a) and a molecule that displays the antigenicity of the infectious agent that causes the infectious disease, in an amount effective to stimulate an immune-response in the subject, such that the infectious disease is treated or prevented. 
     
     
         18 . A method for treating and/or preventing an infectious disease in a subject, wherein the method comprises: (a) decreasing Stat3 expression or function in antigen-presenting cells; (b) culturing the antigen-presenting cells of step (a) and a molecule that displays the antigenicity of the infectious agent that causes the infectious disease to the subject, (c) administering to the subject an amount of the antigen-presenting cells of step (b) effective to stimulate an immune response in the subject, such that the infectious disease is treated or prevented. 
     
     
         19 . A method for treating and/or preventing an infectious disease in a subject, wherein the method comprises administering to the subject an amount of the antigen-presenting cells effective to stimulate an immune response in the subject, wherein the antigen-presenting cells are produced by the following steps: (a) decreasing Stat3 expression or function in antigen-presenting cells; and (b) culturing the antigen-presenting cells of step (a) and a molecule that displays the antigenicity of the infectious agent that causes the infectious disease to the subject, such that the infectious disease is treated or prevented.