Nucleic acid and corresponding protein entitled 158P3D2 useful in treatment and detection of cancer

Abstract

A novel gene (designated 158P3D2) and its encoded protein, and variants thereof, are described wherein 158P3D2 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 158P3D2 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 158P3D2 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 158P3D2 can be used in active or passive immunization.

1 . A composition comprising: 
 a substance that a) modulates the status of 158P3D2, or b) a molecule that is modulated by 158P3D2 whereby the status of a cell that expresses 158P3D2 is modulated.    
     
     
         2 . A composition of  claim 1 , further comprising a physiologically acceptable carrier.  
     
     
         3 . A pharmaceutical composition that comprises the composition of  claim 1  in a human unit dose form.  
     
     
         4 . A composition of  claim 1  wherein the substance comprises an antibody or fragment thereof that specifically binds to a 158P3D2-related protein.  
     
     
         5 . An antibody or fragment thereof of  claim 4 , which is monoclonal.  
     
     
         6 . An antibody of  claim 4 , which is a human antibody, a humanized antibody or a chimeric antibody.  
     
     
         7 . A non-human transgenic animal that produces an antibody of  claim 4 .  
     
     
         8 . A hybridoma that produces an antibody of  claim 5 .  
     
     
         9 . A method of delivering a cytotoxic agent or a diagnostic agent to a cell that expresses 158P3D2, said method comprising: 
 providing the cytotoxic agent or the diagnostic agent conjugated to an antibody or fragment thereof of  claim 4;  and,    exposing the cell to the antibody-agent or fragment-agent conjugate.    
     
     
         10 . A composition of  claim 1  wherein the substance comprises a polynucleotide that encodes an antibody or fragment thereof either of which immunospecifically bind to a 158P3D2-related protein.  
     
     
         11 . A composition of  claim 1  wherein the substance comprises a 158P3D2-related protein.  
     
     
         12 . A protein of  claim 11  that is at least 90% homologous to an entire amino acid sequence shown in FIG. 2 (SEQ ID NOS: ______).  
     
     
         13 . A composition of  claim 1  wherein the substance comprises a peptide of eight, nine, ten, or eleven contiguous amino acids of FIG. 2 or Tables V to XIX, or an analog thereof (SEQ ID NOS: ______).  
     
     
         14 . A composition of  claim 1  wherein the substance comprises a CTL polypeptide of the amino acid sequence of FIG. 2 (SEQ ID NOS: ______).  
     
     
         15 . A composition of  claim 14  further limited by a proviso that the epitope is not an entire amino acid sequence of FIG. 2 (SEQ ID NOS:).  
     
     
         16 . A composition of  claim 14  wherein the substance comprises a CTL polypeptide set forth in Tables V to XIX (SEQ ID NOS: ______).  
     
     
         17 . A composition of  claim 16  further limited by a proviso that the polypeptide is not an entire amino acid sequence of FIG. 2 (SEQ ID NOS: ______).  
     
     
         18 . A composition of  claim 1  wherein the substance comprises an antibody polypeptide epitope of the amino acid sequence of FIG. 2 (SEQ ID NOS: ______).  
     
     
         19 . A composition of  claim 18  further limited by a proviso that the epitope is not an entire amino acid sequence of FIG. 2 (SEQ ID NOS: ______).  
     
     
         20 . A composition of  claim 18  wherein the antibody epitope comprises a peptide region of at least 5 amino acids of FIG. 2 (SEQ ID NOS: ______) in any whole number increment up to 328 that includes an amino acid position selected from: an amino acid position having a value greater than 0.5 in the Hydrophilicity profile of FIG. 5, an amino acid position having a value less than 0.5 in the Hydropathicity profile of FIG. 6; an amino acid position having a value greater than 0.5 in the Percent Accessible Residues profile of FIG. 7; an amino acid position having a value greater than 0.5 in the Average Flexibility profile on FIG. 8; or an amino acid position having a value greater than 0.5 in the Beta-turn profile of FIG. 9.  
     
     
         21 . A composition of  claim 20  further limited by a proviso that the epitope is not an entire amino acid sequence of FIG. 2 (SEQ ID NOS: ______, ______, ______, ______, ______, ______, ______, ______, ______, and ______).  
     
     
         22 . A polynucleotide that encodes a protein of  claim 11 .  
     
     
         23 . A polynucleotide of  claim 22  that comprises a nucleic acid molecule set forth in FIG. 2.  
     
     
         24 . A polynucleotide of  claim 22  further limited by a proviso that the encoded protein is not an entire amino acid sequence of FIG. 2 (SEQ ID NOS: ______).  
     
     
         25 . A polynucleotide of  claim 22  wherein T is substituted with U.  
     
     
         26 . A composition of  claim 1  wherein the substance comprises a polynucleotide comprising a coding sequence of a nucleic acid sequence of FIG. 2 (SEQ ID NOS: ______).  
     
     
         27 . A polynucleotide of  claim 24  further comprising a polynucleotide that encodes a 158P3D2-related protein that is at least 90% homologous to an entire amino acid sequence shown in FIG. 2 (SEQ ID NOS: ______).  
     
     
         28 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 22 .  
     
     
         29 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 25 .  
     
     
         30 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 27 .  
     
     
         31 . A composition of  claim 1  wherein the substance comprises a) a ribozyme that cleaves a polynucleotide having 158P3D2 coding sequence, or b) a nucleic acid molecule that encodes the ribozyme; and, a physiologically acceptable carrier.  
     
     
         32 . A composition comprising the composition of  claim 1  wherein the substance comprises human T cells, wherein said T cells specifically recognize a 158P3D2 peptide sequence in the context of a particular HLA molecule.  
     
     
         33 . A method of inhibiting growth of cancer cells that expresses 158P3D2, the method comprising: 
 administering to the cells the composition of  claim 1 .    
     
     
         34 . A method of  claim 33  of inhibiting growth of cancer cells that express 158P3D2, the method comprising steps of: 
 administering to said cells an antibody or fragment thereof, either of which specifically bind to a 158P3D2-related protein.  
 
     
     
         35 . A method of  claim 33  of inhibiting growth of cancer cells that express 158P3D2, the method comprising steps of: 
 administering to said cells a 158P3D2-related protein.  
 
     
     
         36 . A method of  claim 33  of inhibiting growth of cancer cells that express 158P3D2, the method comprising steps of: 
 administering to said cells a polynucleotide comprising a 158P3D2-related protein coding sequence or a polynucleotide complementary to a polynucleotide having a 158P3D2 coding sequence.  
 
     
     
         37 . A method of  claim 33  of inhibiting growth of cancer cells that express 158P3D2, the method comprising steps of: 
 administering to said cells a ribozyme that cleaves a polynucleotide having 158P3D2 coding sequence.  
 
     
     
         38 . A method of  claim 33  of inhibiting growth of cancer cells that express 158P3D2 and a particular HLA molecule, the method comprising steps of: 
 administering to said cells human T cells, wherein said T cells specifically recognize a 158P3D2 peptide subsequence in the context of the particular HLA molecule.  
 
     
     
         39 . A method of  claim 33 , the method comprising steps of: 
 administering a vector that delivers a single chain monoclonal antibody coding sequence, whereby the encoded single chain antibody is expressed intracellularly within cancer cells that express 158P3D2.    
     
     
         40 . A method of generating a mammalian immune response directed to 158P3D2, the method comprising: 
 exposing cells of the mammal's immune system to a portion of 
 a) a 158P3D2-related protein and/or  
 b) a nucleotide sequence that encodes said protein,  
   whereby an immune response is generated to 158P3D2.    
     
     
         41 . A method of generating an immune response of  claim 40 , said method comprising: 
 providing a 158P3D2-related protein that comprises at least one T cell or at least one B cell epitope; and,    contacting the epitope with a mammalian immune system T cell or B cell respectively, whereby the T cell or B cell is induced.    
     
     
         42 . A method of  claim 41  wherein the immune system cell is a B cell, whereby the induced B cell generates antibodies that specifically bind to the 158P3D2-related protein.  
     
     
         43 . A method of  claim 41  wherein the immune system cell is a T cell that is a cytotoxic T cell (CTL), whereby the activated CTL kills an autologous cell that expresses the 158P3D2-related protein.  
     
     
         44 . A method of  claim 41  wherein the immune system cell is a T cell that is a helper T cell (HTL), whereby the activated HTL secretes cytokines that facilitate the cytotoxic activity of a cytotoxic T cell (CTL) or the antibody-producing activity of a B cell.  
     
     
         45 . A method for detecting the presence of a 158P3D2-related protein or polynucleotide in a sample comprising steps of: 
 contacting the sample with a substance of  claim 1  that specifically binds to the 158P3D2-related protein or polynucleotide, respectively; and,    determining that there is a complex of the substance and 158P3D2-related protein or the substance and 158P3D2-related polynucleotide, respectively.    
     
     
         46 . A method of  claim 45  for detecting the presence of a 158P3D2-related protein in a sample comprising steps of: 
 contacting the sample with an antibody or fragment thereof either of which specifically bind to the 158P3D2-related protein; and,  
 determining that there is a complex of the antibody or fragment thereof and 158P3D2-related protein.  
 
     
     
         47 . A method of  claim 45  further comprising a step of: 
 taking the sample from a patient who has or who is suspected of having cancer.  
 
     
     
         48 . A method of  claim 45  for detecting the presence of 158P3D2 mRNA in a sample comprising: 
 producing cDNA from the sample by reverse transcription using at least one primer;  
 amplifying the cDNA so produced using 158P3D2 polynucleotides as sense and antisense primers, wherein the 158P3D2 polynucleotides used as the sense and antisense primers serve to amplify 158P3D2 cDNA; and,  
 detecting the presence of the amplified 158P3D2 cDNA.  
 
     
     
         49 . A method of  claim 45  for monitoring 158P3D2 gene products in a biological sample from a patient who has or who is suspected of having cancer, the method comprising: 
 determining the status of 158P3D2 gene products expressed by cells in a tissue sample from an individual;  
 comparing the status so determined to the status of 158P3D2 gene products in a corresponding normal sample; and,  
 identifying the presence of aberrant 158P3D2 gene products in the sample relative to the normal sample.  
 
     
     
         50 . A method of monitoring the presence of cancer in an individual comprising: performing the method of  claim 49  whereby the presence of elevated gene products 158P3D2 mRNA or 158P3D2 protein in the test sample relative to the normal tissue sample indicates the presence or status of a cancer.  
     
     
         51 . A method of  claim 50  wherein the cancer occurs in a tissue set forth in Table I.