Compositions and methods for modulating an immune response

Abstract

Described herein are compositions for increasing IL-12 production comprising IgG or a fragment thereof or a variant thereof and uses of said compositions for treating cancer and infectious diseases. Also described herein are compositions for decreasing IL-12 production comprising an agent that inhibits signaling mediated by interaction between FcRn and IgG and uses of said compositions for treating autoimmune diseases. Further described herein are methods for assessing efficacy of treatment by monitoring levels of various cytokines in the subject.

What is claimed: 
     
         1 . A composition for increasing IL-12 production, the composition comprising immunoglobulin G (IgG) or a variant thereof or a fragment thereof. 
     
     
         2 . The composition of  claim 1 , wherein the composition increases signaling mediated by interaction between IgG and FcRn. 
     
     
         3 . The composition of  claim 1 , wherein the composition increases an immune response against an antigen. 
     
     
         4 . The composition of  claim 1 , wherein the variant IgG comprises a methionine to leucine substitution at position 428 and an asparagine to serine substitution at position 434. 
     
     
         5 . The composition of  claim 1 , further comprising an antigen conjugated to IgG or a variant thereof or a fragment thereof so as to create a monomeric or a multimeric structure which can cross-link FcRn. 
     
     
         6 . The composition of  claim 1 , further comprising an antigen complexed to IgG or a variant thereof or a fragment thereof so as to create a multimeric structure which can cross-link FcRn. 
     
     
         7 . The composition of  claim 5 , wherein the antigen is a tumor antigen, an endogenous antigen, a cell-associated antigen, an apoptotic body, a microbial antigen, a viral antigen, a parasitic antigen or a combination thereof. 
     
     
         8 . The composition of  7 , wherein the antigen is a protein or a proteomimetic thereof, a peptide or a peptidomimetic thereof, a lipid or a combination thereof. 
     
     
         9 . The composition of  claim 1 , wherein the IgG or a variant thereof or a fragment thereof is mammalian. 
     
     
         10 . The composition of  claim 1 , wherein the IgG or a variant thereof or a fragment thereof is human. 
     
     
         11 . A composition for decreasing IL-12 production, the composition comprising an agent that inhibits signaling mediated by interaction between FcRn and IgG. 
     
     
         12 . The composition of  claim 11 , wherein the agent is any one or more of a peptide, protein, small molecule, nucleic acid, aptamer, oligonucleotide, antibody or a combination thereof. 
     
     
         13 . The composition of  claim 12 , wherein the nucleic acid is siRNA specific to FcRn. 
     
     
         14 . The composition of  claim 12 , wherein the antibody is selected from the group consisting of a monoclonal antibody or a fragment thereof, a polyclonal antibody or a fragment thereof, chimeric antibody, humanized antibody and single chain antibody. 
     
     
         15 . The composition of  claim 11 , wherein the agent is a bispecific agent comprising binding sites for IgG and FcRn. 
     
     
         16 . The composition of  claim 11 , wherein the agent is a recombinant Fc portion of IgG or a biologically active portion thereof or a proteo-mimetic thereof. 
     
     
         17 . The composition of  claim 16 , wherein the Fc portion of IgG or a biologically active portion thereof is mammalian. 
     
     
         18 . The composition of  claim 16 , wherein the Fc portion of IgG or a biologically active portion thereof is human. 
     
     
         19 . A method for modulating the interaction between FcRn and IgG comprising contacting a cell with an agent that binds FcRn and/or IgG and modulates binding of FcRn to IgG. 
     
     
         20 . The method of  claim 19 , wherein the agent increases signaling mediated by interaction of FcRn and IgG. 
     
     
         21 .- 53 . (canceled)