Nucleic acid and corresponding protein entitled 238P1B2 useful in treatment and detection of cancer

Abstract

A novel gene (designated 238P1B2) and its encoded protein, and variants thereof, are described wherein 238P1B2 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 238P1B2 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 238P1B2 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 238P1B2 can be used in active or passive immunization.

1 . A composition comprising: 
 a substance that modulates the status of 238P1B2, or a molecule that is modulated by 238P1B2 whereby the status of a cell that expresses 238P1B2 is modulated.    
     
     
         2 . The composition of  claim 1 , further comprising a pharmaceutically 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 238P 1B2-related protein.  
     
     
         5 . The antibody or fragment thereof of  claim 4 , which is monoclonal.  
     
     
         6 . The 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 238P1B2, 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 . The composition of  claim 1  wherein the substance comprises a polynucleotide that encodes an antibody or fragment thereof either of which immunospecifically binds to a 238P1B2-related protein.  
     
     
         11 . The composition of  claim 3  wherein the substance comprises a 238P1B2-related protein.  
     
     
         12 . The composition of  claim 1  wherein the substance comprises an analog of a peptide of eight, nine, ten, or eleven contiguous amino acids of FIG. 2A (SEQ ID NO: ______), FIG. 2B (SEQ ID NO: ______), FIG. 2C (SEQ ID NO: ______), FIG. 2D (SEQ ID NO: ______), FIG. 2E (SEQ ID NO: ______), FIG. 2F (SEQ ID NO: ______), or FIG. 2G (SEQ ID NO: ______).  
     
     
         13 . The composition of  claim 1  wherein the substance comprises a CTL polypeptide epitope of FIG. 2A (SEQ ID NO: ______), FIG. 2B (SEQ ID NO: ______), FIG. 2C (SEQ ID NO: ______), FIG. 2D (SEQ ID NO: __), FIG. 2E (SEQ ID NO: ______), FIG. 2F (SEQ ID NO: ______), or FIG. 2G (SEQ ID NO: ______).  
     
     
         14 . A composition of  claim 13  further limited by a proviso that the epitope is not an entire amino acid sequence of FIG. 2A (SEQ ID NO: ______), FIG. 2B (SEQ ID NO: ______), FIG. 2C (SEQ ID NO: ______), FIG. 2D (SEQ ID NO: ______), FIG. 2E (SEQ ID NO: ______), FIG. 2F (SEQ ID NO: ______), or FIG. 2G (SEQ ID NO: ______).  
     
     
         15 . The composition of  claim 13  wherein the substance comprises a CTL polypeptide selected from the amino acid sequence of FIG. 2A (SEQ ID NO: ______), FIG. 2B (SEQ ID NO: ______), FIG. 2C (SEQ ID NO: ______), FIG. 2D (SEQ ID NO: ______), FIG. 2E (SEQ ID NO: ______), FIG. 2F (SEQ ID NO: ______), or FIG. 2G (SEQ ID NO: ______).  
     
     
         16 . A composition of  claim 15  further limited by a proviso that the polypeptide is not an entire amino acid sequence of FIG. 2A (SEQ ID NO: ______), FIG. 2B (SEQ ID NO: ______), FIG. 2C (SEQ ID NO: ______), FIG. 2D (SEQ ID NO: ______), FIG. 2E (SEQ ID NO: ______), FIG. 2F (SEQ ID NO: ______),or FIG. 2G (SEQ ID NO: ______).  
     
     
         17 . The composition of  claim 1  wherein the substance comprises an antibody polypeptide epitope of the amino acid sequence of FIG. 2A (SEQ ID NO: ______), FIG. 2B (SEQ ID NO: ______), FIG. 2C (SEQ ID NO: ______), FIG. 2D (SEQ ID NO: ______), FIG. 2E (SEQ ID NO: ______), FIG. 2F (SEQ ID NO: ______), or FIG. 2G (SEQ ID NO: ______).  
     
     
         18 . A composition of  claim 17  further limited by a proviso that the epitope is not an entire amino acid sequence of FIG. 2A (SEQ ID NO: ______), FIG. 2B (SEQ ID NO: ______), FIG. 2C (SEQ ID NO: ______), FIG. 2D (SEQ ID NO: ______), FIG. 2E (SEQ ID NO: ______), FIG. 2F (SEQ ID NO: ______), or FIG. 2G (SEQ ID NO: ______).  
     
     
         19 . The composition of  claim 18  wherein the antibody epitope comprises a peptide region of at least 5 amino acids of of FIG. 2A (SEQ ID NO: ______), FIG. 2C (SEQ ID NO: ______), FIG. 2D (SEQ ID NO: ______), FIG. 2E (SEQ ID NO: ______), FIG. 2F (SEQ ID NO: ______), or FIG. 2G (SEQ ID NO: ______) in any whole number increment up to 254, or a peptide region of at least 5 amino acids of FIG. 2B (SEQ ID NO: ______) in any whole number increment up to 316, 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.  
     
     
         20 . A composition of  claim 19  further limited by a proviso that the epitope is not an entire amino acid sequence of FIG. 2A (SEQ ID NO: ______), FIG. 2B (SEQ ID NO: ______), FIG. 2C (SEQ ID NO: ______), FIG. 2D (SEQ ID NO: ______), FIG. 2E (SEQ ID NO: ______), FIG. 2F (SEQ ID NO: ______), or FIG. 2G (SEQ ID NO: ______).  
     
     
         21 . A polynucleotide that encodes a peptide of  claim 11 .  
     
     
         22 . The composition of  claim 21  further limited by a proviso that the code sequence is not an entire amino acid sequence of FIG. 2A (SEQ ID NO: ______), FIG. 2B (SEQ ID NO: ______), FIG. 2C (SEQ ID NO: ______), FIG. 2D (SEQ ID NO: ______), FIG. 2E (SEQ ID NO: ______), FIG. 2F (SEQ ID NO: ______), or FIG. 2G (SEQ ID NO: ______).  
     
     
         23 . The composition of  claim 21  wherein T is substituted with U.  
     
     
         24 . The composition of  claim 1  wherein the substance comprises a polynucleotide comprising a coding sequence of FIG. 2A (SEQ ID NO: ______), FIG. 2B (SEQ ID NO: ______), FIG. 2C (SEQ ID NO: ______), FIG. 2D (SEQ ID NO: ______), FIG. 2E (SEQ ID NO: ______), FIG. 2F (SEQ ID NO: ______), or FIG. 2G (SEQ ID NO: ______).  
     
     
         25 . The composition of  claim 22  comprising a polynucleotide that encodes a 238P1B2-related protein that is at least 90% homologous to an entire amino acid sequence shown in FIG. 2A (SEQ ID NO: ______), FIG. 2B (SEQ ID NO: ______), FIG. 2C (SEQ ID NO: ______), FIG. 2D (SEQ ID NO: ______), FIG. 2E (SEQ ID NO: ______), FIG. 2F (SEQ ID NO: ______), or FIG. 2G (SEQ ID NO: ______).  
     
     
         26 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 21 .  
     
     
         27 . A composition comprising a polynucleotide that is filly complementary to a polynucleotide of  claim 23 .  
     
     
         28 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 24 , in human unit dose form.  
     
     
         29 . A composition comprising a polynucleotide that is fully complementary to a polynucleotide of  claim 25 .  
     
     
         30 . A pharmaceutical composition comprising the composition of  claim 1  wherein the substance comprises a ribozyme that cleaves a polynucleotide having 238P1B2 coding sequence or a nucleic acid molecule that encodes the ribozyme and a physiologically acceptable carrier.  
     
     
         31 . A pharmaceutical composition comprising the composition of  claim 1  wherein the substance comprises human T cells, wherein said T cells specifically recognize a 238P1B2 peptide sequence in the context of a particular HLA molecule.  
     
     
         32 . A method of inhibiting growth of cancer cells that expresses 238P1B2, the method comprising: 
 administering to the cells the composition of  claim 1 .    
     
     
         33 . The method of  claim 32  of inhibiting growth of cancer cells that express 238P1B2, the method comprising steps of: 
 administering to said cells an antibody or fragment thereof either of which specifically bind to a 238P1B2-related protein.  
 
     
     
         34 . The method of  claim 32  of inhibiting growth of cancer cells that express 238P1B2, the method comprising steps of: 
 administering to said cells a 23 8P1B2-related protein.  
 
     
     
         35 . The method of  claim 32  of inhibiting growth of cancer cells that express 238P1B2, the method comprising steps of: 
 administering to said cells a polynucleotide comprising a 238P1B2-related protein coding sequence or an antisense polynucleotide complementary to a polynucleotide having a 238P1B132 coding sequence.  
 
     
     
         36 . The method of  claim 32  of inhibiting growth of cancer cells that express 238P1B2, the method comprising steps of: 
 administering to said cells a ribozyme that cleaves a polynucleotide having 238P1B2 coding sequence.  
 
     
     
         37 . The method of  claim 32  of inhibiting growth of cancer cells that express 238P1B2 and a particular HLA molecule, the method comprising steps of: 
 administering to said cells human T cells, wherein said T cells specifically recognize a 238P1B2 peptide sequence in the context of the particular HLA molecule.  
 
     
     
         38 . The method of  claim 32 , 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 238P1B2.    
     
     
         39 . A method of generating a mammalian immune response directed to 238P1B2, the method comprising: 
 exposing cells of the mammal's immune system to an immunogenic portion of 
 a) a 238P1B2-related protein and/or  
 b) a nucleotide sequence that encodes said protein,  
   whereby an immune response is generated to 238P1B2.    
     
     
         40 . The method of inducing an immune response of  claim 39 , said method comprising: 
 providing a 238P1B2-related protein that comprises at least one T cell or at least one B cell epitope;    contacting the epitope with a mammalian immune system T cell or B cell respectively, whereby the T cell or B cell is induced.    
     
     
         41 . The method of  claim 40  wherein the immune system cell is a B cell, whereby the induced B cell generates antibodies that specifically bind to the 238P1B2-related protein.  
     
     
         42 . The method of  claim 40  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 238P1B2-related protein.  
     
     
         43 . The method of  claim 40  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.  
     
     
         44 . An assay for detecting the presence of a 238P1B2-related protein or polynucleotide in a biological sample comprising steps of: 
 contacting the sample with a substance of  claim 1  that specifically binds to the 238P1B2-related protein or polynucleotide, respectively; and,    determining that there is a complex of the substance and 238P1B2-related protein or the substance and 238P1B2-related polynucleotide, respectively.    
     
     
         45 . The assay of  claim 44  for detecting the presence of a 238P1B2-related protein in a biological sample comprising steps of: 
 contacting the sample with an antibody or fragment thereof either of which specifically bind to the 238P1B2-related protein; and,  
 determining that there is a complex of the antibody or fragment thereof and 238P1B2-related protein.  
 
     
     
         46 . The assay of  claim 44  further comprising a step of: 
 taking the sample from a patient who has or who is suspected of having cancer.  
 
     
     
         47 . The assay of  claim 44  for detecting the presence of 238P1B2 mRNA in a biological sample comprising: 
 producing cDNA from the sample by reverse transcription using at least one primer;  
 amplifying the cDNA so produced using 238P1B2 polynucleotides as sense and antisense primers, wherein the 238P1B2 polynucleotides used as the sense and antisense primers are capable of amplifying 238P1B2 cDNA; and  
 detecting the presence of the amplified 238P1B2 cDNA.  
 
     
     
         48 . A method of  claim 44  for monitoring 238P1B2 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 238P1B2 gene products expressed by cells in a tissue sample from an individual;  
 comparing the status so determined to the status of 238P1B2 gene products in a corresponding normal sample; and,  
 identifying the presence of aberrant 238P1B2 gene products in the sample relative to the normal sample.  
 
     
     
         49 . A method of monitoring the presence of cancer in an individual comprising: performing the method of  claim 48  whereby the presence of elevated gene products 238P1B2 mRNA or 238P1B2 protein in the test sample relative to the normal tissue sample indicates the presence or status of a cancer.  
     
     
         50 . The method of  claim 49  wherein the cancer occurs in a tissue set forth in Table I.