Methods of Modulating Immune Function

Abstract

Presented herein are therapeutic agents that modulate one or more immune functions and uses of such therapeutic agents in the prevention, treatment and management of diseases. In one aspect, the therapeutic agents modulate one or more signal transduction pathways induced by the binding of B7-H7 to B7-HrCR, or the binding of B7-H2 to either ICOS, CD28, or CTLA-4. In another aspect, the therapeutic agents modulate the binding of B7-H7 to B7-H7CR, or the binding of B7-H2 to either ICOS, CD28, or CTLA-4. The therapeutic agents can be used in the prevention, treatment and/or management of diseases in which it might be useful to modulate one or more immune functions (e.g., cancer, infectious disease, autoimmune disease, and transplantation rejection). In another aspect, presented herein are methods for identifying receptor-ligand interactions.

1 .- 31 . (canceled) 
     
     
         32 . An antibody or antigen binding fragment thereof that specifically binds to a human B7-H7CR, wherein the human B7-H7CR comprises an amino acid sequence of SEQ ID NO:5 or SEQ ID NO:20, and wherein the antibody or antigen binding fragment thereof is genetically engineered. 
     
     
         33 . The antibody of  claim 32 , wherein the antibody, or antigen binding fragment thereof, agonizes a function of human B7-H7CR upon specifically binding to human B7-H7CR, wherein the function of said human B7-H7CR is:
 (i) binding to the human B7-H7 (SEQ ID NO:3);   (ii) enhancement of a signal transduction pathway inducing activity of the human B7-H7CR;   (iii) enhancement of T lymphocyte proliferation; or   (iv) enhancement of immune function.   
     
     
         34 . The antibody of  claim 32 , wherein the antibody is a monoclonal antibody, or an antigen binding fragment thereof. 
     
     
         35 . The antibody of  claim 32 , wherein the antibody is a humanized antibody, or an antigen binding fragment thereof. 
     
     
         36 . The antibody of  claim 32 , wherein the antibody is a humanized monoclonal antibody, or an antigen binding fragment thereof. 
     
     
         37 . The antibody of  claim 32 , wherein the antibody is a synthetic antibody, or an antigen binding fragment thereof. 
     
     
         38 . The antibody of  claim 32 , wherein the antibody is a bispecific or multispecific antibody, or an antigen binding fragment thereof. 
     
     
         39 . The antibody of  claim 32 , wherein the antibody is a mouse antibody, or an antigen binding fragment thereof. 
     
     
         40 . The antibody of  claim 32 , wherein the antibody is a human antibody, or antigen binding fragment thereof. 
     
     
         41 . The antibody of  claim 32 , wherein the antibody is a chimeric antibody, or an antigen binding fragment thereof. 
     
     
         42 . The non-naturally occurring antibody of  claim 32 , wherein the antibody is an antigen binding fragment of the antibody. 
     
     
         43 . The antibody of  claim 42 , wherein the fragment is selected from the group consisting of single domain antibodies, single-chain Fvs (scFv), single chain antibodies, Fab fragment, F(ab′) fragments, and disulfide-linked bispecific Fvs (sdFv). 
     
     
         44 . The antibody of  claim 32 , wherein the antibody or antigen binding fragment thereof an IgG, IgE, IgM, IgD, IgA or IgY. 
     
     
         45 . The antibody of  claim 44 , wherein the IgG is an IgG1, IgG2, IgG3, or IgG4. 
     
     
         46 . A pharmaceutical composition comprising antibody or antigen binding fragment thereof that specifically binds to a human B7-H7CR, and a pharmaceutically acceptable carrier, wherein the human B7-H7CR comprises an amino acid sequence of SEQ ID NO:5 or SEQ ID NO:20, and wherein the antibody or antigen binding fragment thereof is genetically engineered. 
     
     
         47 . The pharmaceutical composition of  claim 46 , wherein the antibody, or antigen binding fragment thereof, agonizes a function of human B7-H7CR upon specifically binding to human B7-H7CR, wherein the function of said human B7-H7CR is:
 (i) binding to the human B7-H7 (SEQ ID NO:3);   (ii) enhancement of a signal transduction pathway inducing activity of the human B7-H7CR;   (iii) enhancement of T lymphocyte proliferation; or   (iv) enhancement of immune function.   
     
     
         48 . A method for modulating an activity of human B7-H7CR, wherein said method comprises:
 administering a pharmaceutical composition comprising wherein the human B7-H7CR comprises an amino acid sequence of SEQ ID NO:5 or SEQ ID NO:20, and wherein the antibody or antigen binding fragment thereof is genetically engineered, to a subject in need thereof in an amount effective to increase an immune response, wherein the activity of said human B7-H7CR is:   (i) binding to human B7-H7 (SEQ ID NO:3) and the human B7-H7CR;   (ii) enhancement of a signal transduction pathway inducing activity of the human B7-H7CR;   (iii) enhancement of T lymphocyte proliferation; or   (iv) enhancement of immune function.   
     
     
         49 . The method of  claim 48 , wherein said method enhances T lymphocyte proliferation. 
     
     
         50 . The method of  claim 48 , wherein said method enhances immune function. 
     
     
         51 . The method of  claim 48 , wherein said method enhances a signal transduction pathway inducing activity of the human B7-H7CR.