Therapeutic use of anti-CS1 antibodies

Abstract

The present invention is directed to antagonists of CS1 that bind to and neutralize at least one biological activity of CS1. The invention also includes a pharmaceutical composition comprising such antibodies or antigen-binding fragments thereof. The present invention also provides for a method of preventing or treating disease states, including autoimmune disorders and cancer, in a subject in need thereof, comprising administering into said subject an effective amount of such antagonists.

1 . An antibody or an antigen-binding fragment thereof, wherein said antibody binds to CS1 and inhibits immunoglobulin secretion.  
     
     
         2 . The antibody or the antigen-binding fragment according to  claim 1 , wherein said antibody inhibits the proliferation of leukocytes.  
     
     
         3 . The antibody or the antigen-binding fragment according to  claim 1 , wherein said antibody inhibits the proliferation of cancer cells.  
     
     
         4 . The antibody or the antigen-binding fragment according to  claim 1 , wherein said antibody triggers cytotoxic effects on cells expressing CS1 or enhances cytotoxicity mediated by immune cells.  
     
     
         5 . The antibody or antigen binding fragment of  claim 4 , wherein said antibody triggers ADCC-mediated cytotoxicity of cells expressing CS1.  
     
     
         6 . The antibody or the antigen-binding fragment according to  claim 1 , wherein said antibody binds to substantially the same eptitope as the antibody produced by a hybridoma cell line having ATCC accession number PTA-5091 or a Luc63 antibody.  
     
     
         7 . The antibody or antigen-binding fragment according to  claim 1 , wherein said antibody is produced by a hybridoma cell line having ATCC accession number PTA-5091.  
     
     
         8 . The antibody or the antigen-binding fragment according to  claim 1 , wherein said antibody is produced by a hybridoma cell line expressing Luc63 antibody.  
     
     
         9 . The antibody according to  claim 1 , wherein said antibody is a monoclonal antibody.  
     
     
         10 . The antibody according to  claim 9 , wherein said monoclonal antibody is a chimeric antibody, a humanized antibody, or a fully human antibody.  
     
     
         11 . The antibody according to  claim 1 , wherein said antibody is conjugated with a cytotoxic agent.  
     
     
         12 . An antibody or antigen-binding fragment, wherein said antibody binds to substantially the same epitope as an antibody comprising an amino acid sequence of any one of SEQ ID NOS: 3-26.  
     
     
         13 . An antibody or antigen-binding fragment, wherein said antibody comprises an amino acid sequence of any one of SEQ ID NOS: 3-26.  
     
     
         14 . The antibody or the antigen-binding fragment according to  claim 13 , wherein said antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 3 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 4.  
     
     
         15 . The antibody or the antigen-binding fragment according to  claim 13 , wherein said antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 5 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 6.  
     
     
         16 . The antibody or the antigen-binding fragment according to  claim 13 , wherein said antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 8.  
     
     
         17 . A heavy chain complementarity determining region (CDR) of an antibody comprising an amino acid sequence of SEQ ID NOs: 9, 10, 11, 15, 16, 17, 21, 22, or 23.  
     
     
         18 . A light chain complementarity determining region (CDR) of an antibody comprising an amino acid sequence of SEQ ID NOs: 12, 13, 14, 18, 19, 20, 24, 25 or 26.  
     
     
         19 . An antibody or antigen-binding fragment, wherein said antibody comprises an amino acid sequence of any one of SEQ ID NOS: 27-44.  
     
     
         20 . The antibody or antigen-binding fragment of  claim 19 , wherein said antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 27 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 28.  
     
     
         21 . An antibody or antigen binding fragment, wherein said heavy chain variable region comprises a CDR of SEQ ID NO: 33.  
     
     
         22 . A heavy chain complementarity determining region (CDR) of an antibody comprising an amino acid sequence of SEQ ID NOS: 29, 30, 31, 32, or 33.  
     
     
         23 . A light chain complementarity determining region (CDR) of an antibody comprising an amino acid sequence of SEQ ID NOS: 34, 35, 36 or 37.  
     
     
         24 . A pharmaceutical composition comprising a pharmaceutical carrier and the antibody according to  claim 1 .  
     
     
         25 . A method of inhibiting proliferation of CS-1 expressing cells comprising contacting said cells with an effective amount of an antagonist of CS1.  
     
     
         26 . The method according to  claim 25 , wherein said CS-1 expressing cells are plasma cell cancer cells.  
     
     
         27 . The method according to  claim 26 , wherein said plasma cell cancers are selected from the group consisting of multiple myeloma, myeloma of bone, extramedullary plasmacytoma, macroglobulinemia (including Waldenstrom's macroglobulinemia), heavy-chain disease, primary amyloidosis and monoclonal gammopathy of unknown significance.  
     
     
         28 . The method according to  claim 25 , wherein said CS-1 expressing cells are derived from non-plasma cell cancer cells.  
     
     
         29 . The method according to  claim 28 , wherein said non-plasma cell cancer is chronic lymphocytic leukemia.  
     
     
         30 . The method according to  claim 25 , wherein said CS-1 expressing cells are derived from leukocytes.  
     
     
         31 . The method according to  claim 30 , wherein said leukocytes are activated B cells or T cells.  
     
     
         32 . The method according to  claim 31 , wherein said leukocytes are derived from a patient suffering from SLE.  
     
     
         33 . The method according to  claim 25 , wherein said antagonist inhibits immunoglobulin secretion.  
     
     
         34 . The method according to  claim 33 , wherein said inmnunoglobulin is IgG or  
     
     
         35 . The method according to  claim 34 , wherein said antagonist is a protein that directly interacts with CS1.  
     
     
         36 . The method according to  claim 25 , wherein said protein is an antibody or an antigen-binding fragment that binds to CS1.  
     
     
         37 . The method according to  claim 36 , wherein said antibody is monoclonal.  
     
     
         38 . The method according to  claim 37 , wherein said antibody is a chimeric antibody, a humanized antibody, or a fully human antibody.  
     
     
         39 . The method according to  claim 37 , wherein said antibody is conjugated with a cytotoxic agent.  
     
     
         40 . The method according to  claim 37 , wherein said antibody has decreased levels of fucose or is mutated to increase antibody affinity for a FcγR receptor.  
     
     
         41 . The method according to  claim 37 , wherein said antibody is a monoclonal antibody produced by a hybridoma cell line having ATCC accession number PTA-5091.  
     
     
         42 . The method according to  claim 37 , wherein said antibody is a monoclonal antibody produced by a hybridoma cell line expressing Luc63.  
     
     
         43 . The method according to  claim 25 , wherein said antagonist inhibits protein expression of CS1.  
     
     
         44 . The method according to  claim 25 , wherein said antagonist is an anti-sense nucleic acid of a nucleic acid sequence encoding CS1 or a portion thereof.  
     
     
         45 . A method for inhibiting immunoglobulin secretion comprising adminstering an antagonist that specifically binds to a polypeptide encoded by SEQ ID NO:2.  
     
     
         46 . A method for treating an individual with plasma cell cancer comprising administering an antagonist that specifically binds to a polypeptide encoded by SEQ ID NO:2.  
     
     
         47 . The method of  claim 46 , wherein said antagonist is the antibody of  claim 1 .  
     
     
         48 . The method of  claim 46 , wherein said antibody has decreased levels of fucose or is mutated to increase antibody affinity for a FcγR receptor.  
     
     
         49 . The method according to  claim 46 , wherein said plasma cell cancer is myeloma or multiple myeloma.  
     
     
         50 . A method for treating an individual with inflammatory bowel disease comprising administering an antagonist that specifically binds to a polypeptide encoded by SEQ ID NO:2.  
     
     
         51 . A method for increasing ADCC activity of the antibody of  claim 1 , wherein said antibody has decreased levels of fucose or is mutated to increase antibody affinity for a FcγR receptor.