Monoclonal antibodies to interleukin 35 and methods of use thereof to inhibit regulatory t cell function

Abstract

Methods for regulating T cell function in a subject, particularly regulatory T cell activity are provided. Methods of the invention include administering to a subject a therapeutically effective amount of an Interleukin 35-specific binding agent, such as an antibody or small molecule inhibitor. The invention further provides methods for enhancing the immunogenicity of a vaccine or overcoming a suppressed immune response to a vaccine in a subject, including administering to the subject a therapeutically effective amount of an IL35-specific binding agent and administering to the subject a vaccine. In one embodiment the vaccine is a cancer vaccine.

That which is claimed: 
     
         1 . A pharmaceutical composition comprising an excipient and a monoclonal antibody that specifically binds IL35. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the monoclonal antibody specifically binds to the EBI3 subunit of IL35. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the monoclonal antibody specifically binds to the p35 subunit of IL35. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the monoclonal antibody does not specifically bind to IL12 and/or IL27. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the monoclonal antibody specifically binds to the EBI3 subunit of IL35 and specifically blocks IL35 regulatory T-cell activity. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the monoclonal antibody specifically binds to the p35 subunit of IL35 and specifically blocks IL35 regulatory T-cell activity. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the monoclonal antibody specifically interferes with IL35 formation. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the monoclonal antibody is present in the composition in an amount effective to inhibit IL35 immunoregulatory activity. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the monoclonal antibody is present in the composition in an amount effective to reduce and/or block of one or more of the suppressive effects mediated by regulatory T-cells. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the monoclonal antibody is present in the composition in an amount effective to inhibit the activation and/or proliferation of regulatory T-cells relative to the activation and/or proliferation of effector T-cells. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the monoclonal antibody is present in the composition in an amount effective to prevent or overcome induction of tumor antigen tolerance by regulatory T-cells in a subject 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the monoclonal antibody is monovalent, bivalent, or a single chain antibody. 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein the monoclonal antibody is present in the composition in an amount from about 0.1 to about 200 mg/kg body weight in single or divided doses. 
     
     
         14 . A method of inhibiting a regulatory T-cell function in a subject, comprising administering to a subject in need of inhibiting a regulatory T-cell function a therapeutically effective amount of the pharmaceutical composition of  claim 1 , wherein the therapeutically effective amount of said antibody inhibits a regulatory T-cell function in said subject. 
     
     
         15 . A method of inhibiting a regulatory T cell function in a subject, comprising administering to the subject a therapeutically effective amount of a specific binding agent, wherein said specific binding agent binds to IL35. 
     
     
         16 . A method of inhibiting a regulatory T cell function in a subject, comprising administering to the subject a therapeutically effective amount of a specific binding agent, wherein said specific binding agent binds to Interleukin 35 (IL35). 
     
     
         17 . The method of  claim 16 , wherein said specific binding agent comprises an anti-IL35 antibody that specifically binds to IL35. 
     
     
         18 . The method of  claim 16 , wherein said specific binding agent comprises a small molecule inhibitor that specifically binds to IL35. 
     
     
         19 . The method of  claim 18 , wherein said small molecule inhibitor is a chemical compound. 
     
     
         20 . A method of treating a subject having a cancer with a cancer vaccine, comprising:
 (a) administering to the subject a therapeutically effective amount of a specific binding agent, wherein said specific binding agent binds to Interleukin 35 (IL35); and   (b) administering to the subject a cancer vaccine,   wherein said specific binding agent enhances the efficacy of said cancer vaccine.   
     
     
         21 . The method of  claim 20 , wherein said specific binding agent comprises an anti-IL35 antibody that specifically binds to IL35.