Therapeutic and diagnostic methods and compositions targeting 4ig-b7-h3 and its counterpart nk cell receptor

Abstract

The present invention relates to the identification of 4Ig-B7-H3 protein as a tumor associated molecule that imparts protection from NK cell-mediated lysis via a 4Ig-B7-H3 receptor on NK cells. The invention provides compounds that interfere with interactions between the 4Ig-B7-H3 protein and its receptor that can be used to potentiate NK cell cytotoxicity. Also provided are compounds that bind 4Ig-B7-H3-expressing cells so as to inhibit or eliminate them. The compounds are particularly useful in the treatment of tumors, inflammatory conditions, infections and transplantation. Also provided are methods for diagnosing disease by detecting a 4Ig-B7-H3 protein.

We claim: 
     
         1 . A method of killing a tumor cell, the method comprising bringing said cell into contact with a ligand that specifically binds to a 4Ig-B7-H3 polypeptide on a cell surface, wherein the ligand is capable of inducing death of a cell to which it binds. 
     
     
         2 . The method according to  claim 1 , wherein the ligand is an antibody capable of mediating lysis of a cell to which it is bound. 
     
     
         3 . A method of potentiating NK cell activation comprising bringing an NK cell into contact with a composition that blocks an interaction between a 4Ig-B7-H3 polypeptide and a 4Ig-B7-H3 receptor, or between a 4Ig-B7-H3 polypeptide and an NK cell. 
     
     
         4 . An isolated antibody that binds a 4Ig-B7-H3 polypeptide. 
     
     
         5 . The isolated antibody according to  claim 4 , wherein the antibody is 5B14 or 7-517. 
     
     
         6 . An isolated host cell that produces an antibody according to  claim 4 . 
     
     
         7 . The isolated host cell according to  claim 6 , wherein said host cell is a hybridoma. 
     
     
         8 . A composition comprising an antibody according to  claim 4  and a pharmaceutically acceptable carrier.