Gene expressed in prostate cancer and methods of use

Abstract

A polypeptide is disclosed that is specifically detected in the cells of the prostate, termed Splice Variant-Novel Gene Expressed in Prostate (SV-NGEP). Polynucleotides encoding SV-NGEP are also disclosed, as are vectors including these polynucleotides. Host cells transformed with these polynucleotides are also disclosed. Antibodies and immunoconjugates are disclosed that specifically bind SV-NGEP. Methods are disclosed for using an NGEP polypeptide, an antibody that specifically binds SV-NGEP, or a polynucleotide encoding SV-NGEP. Assays are disclosed for the detection prostate cancer. Pharmaceutical compositions including an SV-NGEP polypeptide, an antibody that specifically binds SV-NGEP, or a polynucleotide encoding SV-NGEP are also disclosed. These pharmaceutical compositions are of use in the treatment of prostate cancer.

1 . An isolated antibody that specifically binds
 (i) at least eight consecutive amino acids of amino acids 157-933 of SEQ ID NO: 1, wherein the at least eight consecutive amino acids is eight to ten amino acids in length and binds a Major Histocompatibility Complex (MHC) molecule; or   (ii) an amino acid sequence set forth as SEQ ID NO: 1.   
     
     
         2 . The isolated antibody of  claim 1 , wherein the antibody specifically binds a polypeptide comprising at least eight consecutive amino acids of amino acids 157-933 of SEQ ID NO: 1, wherein the at least eight consecutive amino acids is eight to ten amino acids in length and binds a Major Histocompatibility Complex (MHC) molecule. 
     
     
         3 . The isolated antibody of  claim 1 , wherein the antibody specifically binds a polypeptide comprising an amino acid sequence set forth as SEQ ID NO: 1. 
     
     
         4 . The isolated antibody of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         5 . The isolated antibody of  claim 1  comprising a detectable label. 
     
     
         6 . The isolated antibody of  claim 1  conjugated to a toxin. 
     
     
         7 . A method for detecting prostate cancer in a subject, comprising
 contacting a sample obtained from the subject with the antibody of  claim 1  for a sufficient amount of time to form an immune complex; and   detecting the presence of the immune complex, wherein the presence of an immune complex demonstrates the presence of prostate cancer in the subject.   
     
     
         8 . The method of  claim 7 , wherein the antibody is labeled. 
     
     
         9 . A method for detecting a prostate cancer in a subject, comprising
 contacting a sample from the subject with the antibody of  claim 1  for a sufficient amount of time to form an immune complex; and   detecting the presence of the immune complex, wherein an increase in the presence of the immune complex as compared to a control indicates the presence of the prostate cancer in the subject.   
     
     
         10 . The method of  claim 9 , wherein the sample is a biopsy, blood, serum, or urine sample. 
     
     
         11 . A method for inhibiting the growth of a malignant cell, comprising:
 contacting the malignant cell with an effective amount of a cell-growth inhibiting molecule, wherein the cell growth inhibiting molecule comprises the antibody of  claim 1 ,   wherein the antibody is covalently linked to an effector molecule which inhibits the growth of cells,   thereby inhibiting the growth of the malignant cell.   
     
     
         12 . The method of  claim 11 , wherein the antibody is a monoclonal antibody. 
     
     
         13 . The method of  claim 11 , wherein the effector molecule is a chemotherapeutic agent. 
     
     
         14 . The method of  claim 11 , wherein the effector molecule comprises a toxic moiety. 
     
     
         15 . The method of  claim 11 , wherein the malignant cell is in vivo. 
     
     
         16 . A pharmaceutical composition comprising a therapeutically effective amount of the antibody of  claim 1  in a pharmaceutically acceptable carrier. 
     
     
         17 . A method for reducing the number of prostate cancer cells in a subject, comprising:
 administering to the subject a therapeutically effective amount of the antibody of  claim 1 ,   thereby reducing the number of prostate cancer cells in the subject.   
     
     
         18 . A method for detecting a prostate cancer in a subject, comprising:
 detecting the expression of a polypeptide in a sample from the subject, wherein the polypeptide comprises   (i) at least eight consecutive amino acids of amino acids 157-933 of SEQ ID NO: 1, wherein the polypeptide is eight to ten amino acids in length and binds a Major Histocompatibility Complex (MHC) molecule; or   (ii) an amino acid sequence set forth as SEQ ID NO: 1,   wherein an increase in the expression of the polypeptide as compared to a control indicates the presence of the prostate cancer.   
     
     
         19 . A method for inhibiting the growth of a malignant cell expressing a polypeptide comprising at least eight consecutive amino acids of amino acids 157-933 of SEQ ID NO: 1, wherein the polypeptide is eight to ten amino acids in length and binds a Major Histocompatibility Complex (MHC) molecule; or an amino acid sequence set forth as SEQ ID NO: 1, the method comprising
 (i) culturing cytotoxic T lymphocytes (CTLs) or CTL precursor cells with a polypeptide comprising at least eight consecutive amino acids of amino acids 157-933 of SEQ ID NO: 1, wherein the polypeptide is eight to ten amino acids in length and binds a Major Histocompatibility Complex (MHC) molecule; or an amino acid sequence set forth as SEQ ID NO: 1, to produce activated CTLs or CTL precursors that recognize an NGEP expressing cell, and   (ii) contacting the malignant cell with the activated CTLs or CTLs matured from the CTL precursors,   thereby inhibiting the growth of the malignant cell.   
     
     
         20 . A method for reducing the number of prostate cancer cells in a subject, comprising:
 administering to the subject a therapeutically effective amount of a polypeptide comprising at least eight consecutive amino acids of amino acids 157-933 of SEQ ID NO: 1, wherein the polypeptide is eight to ten amino acids in length and binds a Major Histocompatibility Complex (MHC) molecule; or an amino acid sequence set forth as SEQ ID NO: 1, wherein the administration of the polypeptide results in an immune response to the polypeptide,   thereby reducing the number of prostate cancer cells in the subject.