Compositions and methods for modulating immune responses

Abstract

The present invention provides a newly identified B7 receptor, zB7R1 that functions as lymphocyte inhibitory receptor, which is a PD-1-like molecule and is expressed on T cells. The present invention also provides the discovery of zB7R1's ability to bind to CD155. Methods and compositions for modulating zB7R1-mediated negative signaling and interfering with the interaction of its counter-receptor for therapeutic, diagnostic and research purposes are also provided.

1 . (canceled) 
     
     
         2 . An isolated zB7R1 polypeptide consisting of amino acid residues 16-140 of SEQ ID NO:2. 
     
     
         3 . The isolated zB7R1 polypeptide according to  claim 2 , wherein amino acid residue number 117 of SEQ ID NO:2 is an alanine. 
     
     
         4 . The isolated zB7R1 polypeptide according to  claim 2 , wherein amino acid residue number 117 of SEQ ID NO:2 is a threonine. 
     
     
         5 .- 11 . (canceled) 
     
     
         12 . A fusion protein comprising a polypeptide consisting of amino acid residues 16-140 of SEQ ID NO:2. 
     
     
         13 . The fusion protein according to  claim 12 , wherein the fusion protein further comprises a polyalkyl oxide moiety. 
     
     
         14 . The fusion protein according to  claim 13 , wherein the polyalkyl oxide moiety is polyethylene glycol. 
     
     
         15 . The fusion protein according to  claim 13 , wherein the polyethylene glycol is N-terminally or C-terminally attached to the polypeptide. 
     
     
         16 . The fusion protein according to  claim 13 , wherein the polyethylene glycol is mPEG propionaldehyde. 
     
     
         17 . The fusion protein according to  claim 13 , wherein the polyethylene glycol is branched or linear. 
     
     
         18 . The fusion protein according to  claim 13 , wherein the polyethylene glycol has a molecular weight of about 5 kD, 12 kD, 20 kD, 30 kD, 40 kD or 50 kD. 
     
     
         19 . The fusion protein according to  claim 12 , wherein the fusion protein further comprises an Fc fragment. 
     
     
         20 . The fusion protein according to  claim 19 , wherein the Fc fragment further comprises an immunoglobulin heavy chain constant region of an isotype selected from the group consisting of IgG, IgM, IgE, IgA, and IgD. 
     
     
         21 . The fusion protein according to  claim 20 , wherein the IgG isotype is IgG1, IgG2, IgG3, or IgG4. 
     
     
         22 . The fusion protein according to  claim 12 , wherein the fusion protein comprises a VASP domain. 
     
     
         23 . A formulation comprising:
 an isolated soluble polypeptide consisting of amino acid residues 16-140 of SEQ ID NO:2; and   a pharmaceutically acceptable vehicle.   
     
     
         24 . A kit comprising the formulation of  claim 23 . 
     
     
         25 . A pharmaceutical composition comprising the polypeptide according to  claim 2 . 
     
     
         26 . A formulation comprising:
 a fusion protein comprising a polypeptide consisting of amino acid residues 16-140 of SEQ ID NO:2; and   a pharmaceutically acceptable vehicle.   
     
     
         27 . The formulation according to  claim 26 , wherein the fusion protein further comprises an Fc fragment. 
     
     
         28 . The formulation according to  claim 27 , wherein the Fc fragment further comprises an immunoglobulin heavy chain constant region of an isotype selected from the group consisting of IgG, IgM, IgE, IgA, and IgD. 
     
     
         29 . The formulation according to  claim 28 , wherein the IgG isotype is IgG1, IgG2, IgG3, or IgG4. 
     
     
         30 . The formulation according to  claim 26 , wherein the fusion protein comprises a VASP domain.