Use of bispecific antibodies to regulate immune responses

Abstract

The invention relates generally to the field of immunology, in particular, to bispecific antibodies. Methods for designing a bispecific antibody for use in treating diseases relating to the immune system are disclosed. Specific examples relate to bispecific antibodies which recognize an activating receptor and an inhibiting receptor.

What is claimed is:  
     
         1 . A method for using a bispecific antibody to reduce the activity of a cell or of an activating receptor, wherein said bispecific antibody binds to: 
 (a) an activating receptor; and    (b) an inhibiting receptor.    
     
     
         2 . The method of  claim 1 , wherein the inhibiting receptor contains an ITIM motif.  
     
     
         3 . The method of  claim 1 , wherein the inhibiting receptor is selected from the group consisting of FcγRIIB, LAIR-1, KIR, OX2R, OX2Ra, DSP-1, CD5, MAFA, CTLA-4, HM18, Ly49, and gp49B1.  
     
     
         4 . The method of  claim 1 , wherein the activating receptor contains an ITAM motif.  
     
     
         5 . The method of  claim 1 , wherein the activating receptor is selected from the group consisting of FcεRI, FcγRIII, FcγRIIA, FcγRIIC, T-cell receptor, TREM-1, TREM-2, CD28, CD3, CD2, and DAP-12.  
     
     
         6 . The method of  claim 1 , wherein the activating receptor is FcεRI and the inhibiting receptor is OX2Ra.  
     
     
         7 . The method of  claim 1 , wherein the bispecific antibody comprises a chemical linking agent that is covalently incorporated into the bispecific antibody.  
     
     
         8 . The method of  claim 1 , wherein said bispecific antibody is a single polypeptide chain antibody.  
     
     
         9 . The method of  claim 1 , wherein the bispecific antibody is humanized.  
     
     
         10 . The method of  claim 1 , wherein the bispecific antibody is administered in conjunction with an agent that stimulates expression of an inhibiting receptor or an activating receptor.  
     
     
         11 . The method of  claim 10 , wherein said agent is selected from the group consisting of granulocyte colony stimulating factor and interferon-γ.  
     
     
         12 . The method of  claim 1 , wherein the bispecific antibody is administered in conjunction with a therapeutic selected from the group consisting of an antiinflammatory agent, a chemotherapeutic agent, an immunosuppressive agent, and an anti-malarial agent.  
     
     
         13 . The method of  claim 12 , wherein the antiinflammatory agent is selected from the group consisting of corticosteroids, glucocorticoids, soluble tumor necrosis factor receptor, and antibodies against tumor necrosis factor.  
     
     
         14 . The method of  claim 12 , wherein the chemotherapeutic agent is selected from the group consisting of methotrexate, vincristine, and cyclophosphamide.  
     
     
         15 . A composition comprising the bispecific antibody of  claim 1  in conjunction with an acceptable carrier.  
     
     
         16 . The method of  claim 1 , wherein said administration is in vivo or to cultured cells.  
     
     
         17 . A kit comprising: 
 (a) the bispecific antibody of  claim 1  in a compartment; and    (b) instructions for use.