Use of NRG4, or inhibitors thereof, in the treatment of colon and pancreatic cancers

Abstract

This invention relates to compositions and uses of NRG4, and to variants thereof and to polynucleotides encoding NRG4, for therapeutic and diagnostic purposes, particularly related to colon and pancreatic cancer. This invention also relates to therapeutic agents based on or derived from the polynucleotides and proteins, NRG4 inhibitors, particularly antibodies capable of specifically binding to NRG4.

1 . A method of treating colon cancer in a human subject, the method comprising administering to the subject an effective amount of an antibody that specifically binds an NRG4 polypeptide.  
     
     
         2 . The method of  claim 1  wherein the NRG4 polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NO:2 or an immunologically active fragment thereof.  
     
     
         3 . The method of  claim 1  wherein the NRG4 polypeptide comprises an amino acid sequence at least 99% identical to SEQ ID NO:2 or an immunologically active fragment thereof.  
     
     
         4 . The method of  claim 1  wherein the NRG4 polypeptide comprises the amino acid sequence of SEQ ID NO:2 or an immunologically active fragment thereof.  
     
     
         5 . The method of  claim 1  wherein the NRG4 polypeptide comprises at least 20 contiguous amino acids of SEQ ID NO:2.  
     
     
         6 . The method of  claim 1  wherein the NRG4 polypeptide comprises at least 50 contiguous amino acids of SEQ ID NO:2  
     
     
         7 . The method of  claim 1  wherein the NRG4 polypeptide comprises residues 4 to 50 of SEQ ID NO:2.  
     
     
         8 . The method of  claim 1  wherein the NRG4 polypeptide comprises residues 9 to 45 of SEQ ID NO:2.  
     
     
         9 . The method of  claim 1  wherein the antibody is a monoclonal antibody, a polyclonal antibody, a human antibody, humanized antibody, a chimeric antibody, a single chain antibody, a F(ab) fragment, or a F(ab′) 2  fragment.  
     
     
         10 . The method of  claim 1  wherein the antibody is a monoclonal antibody.  
     
     
         11 . The method of  claim 10  wherein the monoclonal antibody binds to the NRG4 polypeptide with an affinity of at least 10 7  M −1 .  
     
     
         12 . The method of  claim 1  wherein the antibody is labeled.  
     
     
         13 . The method of  claim 12  wherein the label is an enzyme or a cytotoxic agent.  
     
     
         14 . The method of  claim 12  wherein the label is a reporter molecule selected from the group consisting of a dye, radionuclide, luminescent group, fluorescent group, or biotin.  
     
     
         15 . The method of  claim 13  wherein the cytotoxic agent is a toxin, a chemotherapeutic agent, an anti-mitotic agent or an antibiotic.  
     
     
         16 . A method of inhibiting proliferation of a colon cancer cell, the method comprising contacting the colon cancer cell with an antibody which specifically binds to an NRG4 polypeptide.  
     
     
         17 . A method for decreasing NRG4 polypeptide activity in a human subject, the method comprising administering to the subject an effective amount of an antibody that specifically binds an NRG4 polypeptide.  
     
     
         18 . The method of  claim 17  wherein the subject has colon cancer.  
     
     
         19 . The method of  claim 16  or  17  wherein the NRG4 polypeptide comprises an amino acid sequence at least 98% identical to SEQ ID NO:2 or an immunologically active fragment thereof.  
     
     
         20 . The method of  claim 16  or  17  wherein the NRG4 polypeptide comprises the amino acid sequence of SEQ ID NO:2 or an immunologically active fragment thereof.