Compositions and methods for prostate cancer analysis

Abstract

The invention provides methods for diagnosing prostate cancer. The invention also provides novel anti-STEAP-1 antibodies and uses thereof.

What is claimed is: 
     
         1 . A method for diagnosing prostate cancer in a test subject, comprising:
 a) contacting cancer cells of epithelial origin with an antibody that specifically binds to a prostate-specific marker, wherein the cancer cells are from a blood sample taken from the test subject; and   b) determining whether any of the cancer cells express the prostate-specific marker, wherein the presence of cancer cells that express the prostate-specific marker is predictive of having prostate cancer in the test subject.   
     
     
         2 . The method of  claim 1 , further comprising determining the amount of the cancer cells that express the prostate-specific marker, wherein such amount is predictive of the stage of prostate cancer in the test subject. 
     
     
         3 . The method of  claim 1 , further comprising determining the expression level of the prostate-specific marker on the cancer cells. 
     
     
         4 . The method of  claim 1 , further comprising grading the cancer cells based on their expression level of the prostate-specific marker, and determining the percentage of the cancer cells in each grade. 
     
     
         5 . The method of  claim 1 , further comprising calculating a grade score for each grade by multiplying the percentage of the cancer cells in said grade with a unique grade number representative of the expression level of the prostate-specific marker in said grade, and summing up all the grade scores to obtain an H score, wherein the H score is indicative of the stage of the prostate cancer in the test subject. 
     
     
         6 . The method of  claim 1 , wherein the cancer cells are identified from the blood sample with a capturing composition comprising a ligand that specifically binds to cancer cells of epithelial origin. 
     
     
         7 . The method of  claim 6 , wherein the ligand is an antibody that specifically binds to an epithelial antigen preferentially expressed on cancer cells. 
     
     
         8 . The method of  claim 7 , wherein the epithelial antigen is Epithelial Cell Adhesion Molecule (EpCAM). 
     
     
         9 . The method of  claim 6 , wherein the identified cancer cells are enriched in a cell fraction separated from the blood sample. 
     
     
         10 . The method of  claim 9 , wherein the cell fraction is separated under a magnetic field. 
     
     
         11 . The method of  claim 10 , wherein the ligand in the capturing composition is coupled to a magnetic particle. 
     
     
         12 . The method of  claim 11 , wherein the ligand comprises an EpCAM antibody. 
     
     
         13 . The method of  claim 1 , wherein the prostate-specific marker is selected from the group consisting of: a Six-Transmembrane Epithelial Antigen of the Prostate (STEAP), Prostate-specific membrane antigen (PSMA), Prostate carcinoma tumor antigen (PCTA-1), and Prostate stem cell antigen (PSCA). 
     
     
         14 . The method of  claim 1 , wherein the antibody that specifically binds to a prostate-specific marker comprises an anti-STEAP-1 antibody. 
     
     
         15 . The method of  claim 14 , wherein the anti-STEAP-1 antibody binds to STEAP-1 with a K D  of ≦1000 nM. 
     
     
         16 . The method of  claim 14 , wherein the anti-STEAP- 1  antibody is a polyclonal antibody or a monoclonal antibody. 
     
     
         17 . The method of  claim 16 , wherein the anti-STEAP-1 antibody is a murine monoclonal antibody. 
     
     
         18 . The method of  claim 17 , wherein the anti-STEAP-1 antibody is 15A5, produced by a hybridoma cell having a microorganism deposit number of PTA-12259. 
     
     
         19 . The method of  claim 14 , wherein the anti-STEAP-1 antibody is conjugated with a first detectable label. 
     
     
         20 . The method of  claim 1 , wherein the cancer cells are identified with one or more reagents that allow detection of cancer cells of epithelial origin. 
     
     
         21 . The method of  claim 20 , wherein the reagents comprise a ligand that specifically binds to a cytokeratin, and wherein the ligand is optionally conjugated with a second detectable label. 
     
     
         22 . The method of  claim 21 , wherein the reagents further comprise a dye that differentiates cells from non-cell components. 
     
     
         23 . The method of  claim 22 , wherein the dye is 4′,6-diamidino-2-phenylindole (DAPI). 
     
     
         24 . The method of  claim 23 , wherein the reagents further comprise a ligand that specifically binds to a leukocyte marker, and wherein the ligand is optionally conjugated with a third detectable label. 
     
     
         25 . The method of  claim 24 , wherein the ligand to a leukocyte marker is a CD45 antibody. 
     
     
         26 . The method of  claim 1 , wherein the determining is by a method based on immunofluorescent microscopy, flow cytometry, fiber-optic scanning cytometry, or laser scanning cytometry. 
     
     
         27 . A method of predicting efficacy of prostate cancer therapy in a test subject, comprising:
 a) contacting cancer cells of epithelial origin with an antibody that specifically binds to a prostate-specific marker, wherein the cancer cells are from a blood sample taken from the test subject; and   b) determining whether any of the cancer cells express the prostate-specific marker, wherein the presence of cancer cells that express the prostate-specific marker is predictive of the efficacy of the prostate cancer therapy in the test subject.   
     
     
         28 . A method of monitoring response to a prostate cancer therapy in a test subject, comprising:
 a) contacting a first group of cancer cells of epithelial origin with an antibody that specifically binds to a prostate-specific marker, wherein the first group of cancer cells are from a first blood sample taken from the test subject;   b) determining the amount of the cancer cells in the first group that express prostate-specific marker and/or the expression level of the prostate-specific marker in the cancer cells;   c) contacting a second group of cancer cells of epithelial origin with the antibody that specifically binds to a prostate-specific marker, wherein the second group of cancer cells are from a second blood sample taken from the test subject after a test period of prostate cancer therapy;   d) determining the amount of the cancer cells in the second group that express prostate-specific marker and/or the expression level of the prostate-specific marker in the cancer cells; and   e) comparing the amount of the cancer cells that express the prostate-specific marker and/or the prostate-specific marker expression level as determined in b) with that in d), wherein a decrease in the amount of the cancer cells expressing the prostate-specific marker and/or a decrease in the prostate-specific marker expression level in the cancer cells indicates a response to the prostate cancer therapy in the test subject.   
     
     
         29 . The method of  claim 27 , wherein the prostate cancer therapy comprises an antibody or antibody-drug conjugate (ADC) that binds to the prostate-specific marker. 
     
     
         30 . The method of  claim 29 , wherein the prostate-specific marker is STEAP-1. 
     
     
         31 . The method of  claim 30 , wherein the ADC comprises an anti-STEAP-1 antibody covalently attached to a cytotoxic agent. 
     
     
         32 . The method of  claim 31 , wherein the cytotoxic agent is selected from a toxin, a chemotherapeutic agent, a drug moiety, monomethylauristatin E (MMAE), an antibiotic, a radioactive isotope, and a nucleolytic enzyme. 
     
     
         33 . An antibody which binds to substantially the same epitope to which antibody 15A5 binds, wherein antibody 15A5 is produced by a hybridoma cell having a microorganism deposit number of: PTA-12259. 
     
     
         34 . The antibody of  claim 33 , which comprises at least one of the CDR regions of the antibody 15A5. 
     
     
         35 . The antibody of  claim 34 , which comprises the six CDR regions of the antibody 15A5. 
     
     
         36 . The antibody of  claim 33 , which comprises the heavy chain variable region of the antibody 15A5. 
     
     
         37 . The antibody of  claim 33 , which comprises the light chain variable region of the antibody 15A5. 
     
     
         38 . The antibody of  claim 33 , which is antibody 15A5 or an antigen binding fragment thereof. 
     
     
         39 . The antibody of  claim 38 , further conjugated to a detectable label. 
     
     
         40 . An isolated polynucleotide encoding the antibody of  claim 35 . 
     
     
         41 . A host cell comprising the polynucleotide of  claim 40 . 
     
     
         42 . A hybridoma cell line having a microorganism deposit number of PTA-12259. 
     
     
         43 . Use of the antibody of  claim 33  or an antigen-binding fragment thereof in the manufacture of a diagnostic agent for prostate cancer. 
     
     
         44 . A test kit for detecting presence of prostate cancer cells expressing STEAP-1 in a blood sample, comprising an antibody that specifically binds to STEAP-1. 
     
     
         45 . The test kit of  claim 44 , wherein the antibody is conjugated with a detectable label. 
     
     
         46 . The test kit of  claim 44 , wherein the antibody is an antibody of  claim 33 .