Novel tumor antigen useful in diagnosis and therapy of prostate and colon cancer

Abstract

Compositions for the diagnosis and therapy of prostate and colon cancer, derived from or based on a novel prostate-specific, androgen-regulated, cell membrane associated and secreted serine protease termed 20P1F12/TMPRSS2 are described. A full length cDNA comprising the entire coding sequence of the 20P1F12/TMPRSS2 gene (also designated 20P1F12-GTC1 herein) is provided (FIG. 1 ). Among the compositions provided are antibodies that bind to 20P1F12/TMPRSS2 proteins and polypeptide fragments thereof, including antibodies labeled with a detectable marker or toxin or therapeutic composition. The invention also provides prognostic and diagnostic methods of examining a biological sample for evidence of disregulated cellular growth by comparing the status of 20P1F12/TMPRSS2 in the biological sample to the status of 20P1F12/TMPRSS2 in a corresponding normal sample, wherein alterations in the status of 20P1F12/TMPRSS2 in the biological sample are associated with disregulated cellular growth. The invention further provides various therapeutic compositions and strategies for treating prostate cancer, including particularly, 20P1F12/TMPRSS2 polypeptide and anti-20P1F12/TMPRSS2 antibody therapy methods and compositions, cancer vaccines, and small molecule therapy.

1 - 19 . (canceled)  
     
     
         20 . A method of detecting a cancer in an individual comprising: 
 (a) examining 20P1F12/TMPRSS2 gene expression in a test biological sample obtained from the individual; and    (b) examining the individual for the presence of a factor associated with disregulated cellular growth;    wherein a coincidence of 20P1F12/TMPRSS2 gene expression in the test biological sample obtained from the individual and the presence of the factor associated with disregulated cellular growth is indicative of the cancer.    
     
     
         21 . The method according to  claim 20 , wherein the cancer is a prostate cancer.  
     
     
         22 . The method according to  claim 20 , wherein the cancer is a colon cancer.  
     
     
         23 . The method according to  claim 20 , wherein the factor associated with disregulated cellular growth is an increase in the level of prostate specific antigen expression.  
     
     
         24 . The method according to  claim 20 , wherein the test biological sample is selected from the group consisting of blood, serum, stool, urine, semen and biopsied tissue.  
     
     
         25 . The method according to  claim 20 , wherein the 20P1F12/TMPRSS2 gene expression in the test biological sample is evaluated by examining the level of 20P1F12/TMPRSS2 mRNA expression or the level of 20P1F12/TMPRSS2 polypeptide expression.  
     
     
         26 . The method according to  claim 20 , wherein the 20P1F12/TMPRSS2 gene expression in the test biological sample is evaluated by a method selected from the group consisting of Southern analysis, northern analysis, polymerase chain reaction analysis and immunoassay.  
     
     
         27 . The method of  claim 20 , wherein the 20P1F12/TMPRSS2 gene expression in a test biological sample is evaluated by an immunoassay which measures the concentration of free 20P1F12/TMPRSS2 polypeptide or the concentration of 20P1F12/TMPRSS2 polypeptide complexed to a binding partner.  
     
     
         28 . The method of  claim 27 , wherein the 20P1F12/TMPRSS2 evaluated in the test biological sample is secreted from cells exhibiting disregulated growth.  
     
     
         29 . A method of inhibiting the growth of a neoplastic cell that expresses 20P1F12/TMPRSS2 comprising contacting the 20P1F12/TMPRSS2 expressed by the neoplastic cell with an effective amount of an anti-20P1F12/TMPRSS2 antibody so that the growth of the neoplastic cell is inhibited.  
     
     
         30 . A method of inhibiting the progression of a neoplasm that expresses 20P1F12/TMPRSS2 comprising contacting the 20P1F12/TMPRSS2 expressed by the neoplasm with an effective amount of an anti-20P1F12/TMPRSS2 antibody so that the progression of a neoplasm is inhibited.  
     
     
         31 . The method of  claim 30 , wherein the antibody binds an epitope within a predominantly cell surface associated domain of 20P1F12/TMPRSS2.  
     
     
         32 . The method of  claim 31 , wherein the antibody is coupled to a cytotoxic agent.  
     
     
         33 - 38 . (canceled)