Novel serpentine transmembrane antigens expressed in human cancers and uses thereof

Abstract

Described is a novel family of cell surface serpentine transmembrane antigens. Two of the proteins in this family are exclusively or predominantly expressed in the prostate, as well as in prostate cancer, and thus members of this family have been termed “STEAP” (Six Transmembrane Epithelial Antigens of the Prostate). Four particular human STEAPs are described and characterized herein. The prototype member of the STEAP family, STEAP-1, appears to be a type IIIa membrane protein expressed predominantly in prostate cells in normal human tissues. Structurally, STEAP-1 is a 339 amino acid protein characterized by a molecular topology of six transmembrane domains and intracellular N- and C-termini, suggesting that it folds in a “serpentine” manner into three extracellular and two intracellular loops. STEAP-1 protein expression is maintained at high levels across various stages of prostate cancer. Moreover, STEAP-1 is highly over-expressed in certain other human cancers.

1 . A method for generating an immune response to STEAP-2 in a mammal, comprising:
 a) contacting a cell of the mammal's immune system with an immunogenic portion of:
 i) a protein having at least 90% homology to SEQ ID NO: 6; and/or 
 ii) a nucleotide sequence that encodes said protein; and 
   b) inducing the cell to produce a response to the protein.   
     
     
         2 . The method of  claim 1 , wherein the protein having at least 90% homology to SEQ ID NO: 6 comprises at least one T cell epitope or at least one B cell epitope. 
     
     
         3 . The method of  claim 1 , wherein the cell is a B cell. 
     
     
         4 . The method of  claim 3 , wherein the response comprises generating an antibody from the B cell that specifically binds to the protein having at least 90% homology to SEQ ID NO: 6. 
     
     
         5 . The method of  claim 1 , wherein the cell is a cytotoxic T cell. 
     
     
         6 . The method of  claim 5 , wherein the response comprises killing by the cytotoxic T cell of an autologous cell that expresses the protein having at least 90% homology to SEQ ID NO: 6. 
     
     
         7 . The method of  claim 1 , wherein the cell is a helper T cell. 
     
     
         8 . The method of  claim 7  wherein the response comprises secretion of cytokines from the helper T cell that facilitate the cytotoxic activity of a cytotoxic T cell or the antibody producing activity of a B cell. 
     
     
         9 . The method of  claim 4 , wherein the antibody is domain-specific. 
     
     
         10 . The method of  claim 1 , wherein the protein is expressed in a viral vector. 
     
     
         11 . The method of  claim 1 , wherein the nucleotide sequence is expressed in a viral vector. 
     
     
         12 . The method of  claim 11 , wherein the nucleotide sequence is at least 90% identical to SEQ ID NO: 7. 
     
     
         13 . The method of  claim 11 , wherein the nucleotide sequence is SEQ ID NO: 7. 
     
     
         14 . A method for inducing a cellular immune response in a subject to a protein having at least 90% homology to SEQ ID NO: 6 in a subject having a cancer expressing STEAP-2 protein, comprising administering to the subject a STEAP-2 protein or fragment thereof, or a STEAP-2 antigen presenting cell. 
     
     
         15 . The method of  claim 14 , wherein the cancer is a cancer set forth in Table I. 
     
     
         16 . The method of  claim 14 , wherein the step of administering generates a humoral immune response. 
     
     
         17 . The method of  claim 14 , wherein the STEAP-2 antigen presenting cell is a dendritic cell.