T cell inhibitory receptor compositions and uses thereof

Abstract

The invention relates to compositions which bind T cell inhibitory receptor molecules and modulate T cell activity, and methods of using such compositions. Such compositions include biliary glycoprotein binding agents. Methods for modulating killer T cell activities, including cytotoxicity and proliferation also are provided.

1 . A method for the treatment of an autoimmune disease, immunodeficiency, cancer, transplant rejection, disorders involving invasion by microorganisms or undesirable cell growth comprising
 administering to a subject in need of such treatment a molecule that binds biliary glycoprotein, wherein the molecule is an antibody or an antigen-binding fragment thereof; a ligand for biliary glycoprotein or a fragment thereof that binds biliary glycoprotein; or a fusion protein containing a biliary glycoprotein ligand or other biliary glycoprotein binding molecule.   
     
     
         2 . The method of  claim 1 , wherein the molecule that binds biliary glycoprotein is an antibody that specifically binds biliary glycoprotein or an antigen-binding fragment thereof. 
     
     
         3 . The method of  claim 2 , wherein the antigen-binding fragment is a Fab fragment. 
     
     
         4 . The method of  claim 2 , wherein the antibody is a monoclonal antibody or binding fragment thereof. 
     
     
         5 . The method of  claim 1 , wherein the molecule that binds biliary glycoprotein is a ligand for biliary glycoprotein or a fragment thereof that binds biliary glycoprotein. 
     
     
         6 . The method of  claim 5 , wherein the biliary glycoprotein is a soluble biliary glycoprotein molecule or a fragment thereof. 
     
     
         7 . The method of  claim 5 , wherein the fragment of biliary glycoprotein is the N-domain of CD66a, the NA I B1 domains of CD66a or the NA1B1A2 domains of CD66a. 
     
     
         8 . The method of  claim 1 , wherein the molecule that binds biliary glycoprotein is a fusion protein containing a biliary glycoprotein ligand or other biliary glycoprotein binding molecule. 
     
     
         9 . The method of  claim 8 , wherein the fusion protein comprises a biliary glycoprotein polypeptide or a fragment thereof fused to an immunoglobulin molecule or a fragment thereof. 
     
     
         10 . The method of  claim 9 , wherein the fragment of biliary glycoprotein is the N-domain of CD66a, the NA1 B1 domains of CD66a or the NA1B1A2 domains of CD66a. 
     
     
         11 . The method of  claim 9 , wherein the fragment of the immunoglobulin molecule is the Fe portion of the immunoglobulin molecule. 
     
     
         12 . The method of  claim 1 , wherein the molecule that binds biliary glycoprotein binds two or more biliary glycoprotein polypeptides. 
     
     
         13 . The method of  claim 1 , wherein the molecule that binds biliary glycoprotein binds only a single biliary glycoprotein polypeptide.