Compositions and methods for the diagnosis and treatment of tumor

Abstract

The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.

What is claimed is: 
     
         1 . An isolated antibody comprising at least one CDR sequence selected from the group consisting of:
 (a) a CDR-L1 sequence of any one of SEQ ID NOS:21-34;   (b) a CDR-L2 sequence of any one of SEQ ID NOS:35-38;   (c) a CDR-L3 sequence of any one of SEQ ID NOS:39-41;   (d) a CDR-H1 sequence of any one of SEQ ID NOS:42-45;   (e) a CDR-H2 sequence of any one of SEQ ID NOS:46-60; and   (f) a CDR-H3 sequence of any one of SEQ ID NOS:61-65.   
     
     
         2 . The isolated antibody of  claim 1  further comprising a VH acceptor human consensus framework sequence of any one of SEQ ID NOS:66-75. 
     
     
         3 . The isolated antibody of  claim 1  further comprising a VL acceptor human consensus framework sequence of any one of SEQ ID NOS:76-79. 
     
     
         4 . The isolated antibody of  claim 1  further comprising a VH acceptor human consensus framework sequence of any one of SEQ ID NOS:66-75 and a VL acceptor human consensus framework sequence of any one of SEQ ID NOS:76-79. 
     
     
         5 . The antibody of  claim 1  which is an antibody fragment. 
     
     
         6 . The antibody of  claim 1  which is a chimeric or a humanized antibody. 
     
     
         7 . The antibody of  claim 1  which is conjugated to a growth inhibitory agent. 
     
     
         8 . The antibody of  claim 1  which is conjugated to a cytotoxic agent. 
     
     
         9 . The antibody of  claim 8 , wherein the cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 
     
     
         10 . The antibody of  claim 8 , wherein the cytotoxic agent is a toxin. 
     
     
         11 . The antibody of  claim 10 , wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin. 
     
     
         12 . The antibody of  claim 10 , wherein the toxin is a maytansinoid. 
     
     
         13 . The antibody of  claim 1  which is produced in bacteria. 
     
     
         14 . The antibody of  claim 1  which is produced in CHO cells. 
     
     
         15 . The antibody of  claim 1  which induces death of a cell to which it binds. 
     
     
         16 . The antibody of  claim 15 , wherein said cell is an ovarian cancer cell. 
     
     
         17 . The antibody of  claim 15 , wherein said cell is a lung cancer cell. 
     
     
         18 . The antibody of  claim 1  which is detectably labeled. 
     
     
         19 . An isolated antibody comprising a VL sequence of any shown in SEQ ID NOS:6-11. 
     
     
         20 . An isolated antibody comprising a VH sequence of any shown in SEQ ID NOS:15-20. 
     
     
         21 . An isolated antibody comprising the VL sequence of SEQ ID NO:6 and a VH sequence of SEQ ID NO:15. 
     
     
         22 . An isolated antibody comprising the VL sequence of SEQ ID NO:7 and a VH sequence of SEQ ID NO:16. 
     
     
         23 . An isolated antibody comprising the VL sequence of SEQ ID NO:8 and a VH sequence of SEQ ID NO:17. 
     
     
         24 . An isolated antibody comprising the VL sequence of SEQ ID NO:9 and a VH sequence of SEQ ID NO:18. 
     
     
         25 . An isolated antibody comprising the VL sequence of SEQ ID NO:10 and a VH sequence of SEQ ID NO:19. 
     
     
         26 . An isolated antibody comprising the VL sequence of SEQ ID NO:11 and a VH sequence of SEQ ID NO:20. 
     
     
         27 . An isolated antibody comprising the heavy chain sequence of SEQ ID NO:80. 
     
     
         28 . An isolated antibody comprising the light chain sequence of SEQ ID NO:81. 
     
     
         29 . An isolated antibody comprising the heavy chain sequence of SEQ ID NO:80 and the light chain sequence of SEQ ID NO:81. 
     
     
         30 . A cell which produces an antibody of  claim 1 . 
     
     
         31 . An isolated nucleic acid that encodes an antibody of  claim 1 . 
     
     
         32 . A method of identifying a first antibody that binds to a TAT211 antigenic epitope bound by a second antibody, wherein said second antibody is an antibody according to  claim 1 , said method comprising determining the ability of said first antibody to block binding of said second antibody to a TAT211 polypeptide, wherein the ability of said first antibody to block the binding of said second antibody to said TAT211 polypeptide by at least 40% and at equal antibody concentrations is indicative of said first antibody being capable of binding to an epitope bound by said second antibody. 
     
     
         33 . A method of inhibiting the growth of a cell that expresses a TAT211 polypeptide, said method comprising contacting said cell with an antibody according to  claim 1 , wherein the binding of said antibody to said TAT211 polypeptide causes an inhibition of growth of said cell. 
     
     
         34 . The method of  claim 33 , wherein said TAT211 polypeptide comprises the amino acid sequence of SEQ ID NO:2 or an extracellular domain thereof. 
     
     
         35 . The method of  claim 33 , wherein said cell is an ovarian cancer cell. 
     
     
         36 . The method of  claim 33 , wherein said cell is a lung cancer cell. 
     
     
         37 . A method of therapeutically treating a mammal having a cancerous tumor comprising cells that express a TAT211 polypeptide, said method comprising administering to said mammal a therapeutically effective amount of an antibody according to  claim 1 , thereby effectively treating said mammal. 
     
     
         38 . The method of  claim 37 , wherein said TAT211 polypeptide comprises the amino acid sequence of SEQ ID NO:2 or an extracellular domain thereof. 
     
     
         39 . The method of  claim 37 , wherein said cells are ovarian cancer cells. 
     
     
         40 . The method of  claim 37 , wherein said cells are lung cancer cells. 
     
     
         41 . A method of determining the presence of a TAT211 protein in a sample suspected of containing said protein, said method comprising exposing said sample to an antibody of  claim 1  and determining binding of said antibody to said protein in said sample, wherein binding of the antibody to said protein is indicative of the presence of said protein in said sample. 
     
     
         42 . The method of  claim 41 , wherein said sample comprises a cell suspected of expressing said protein. 
     
     
         43 . The method of  claim 42 , wherein said cell is an ovarian cancer cell. 
     
     
         44 . The method of  claim 42 , wherein said cell is a lung cancer cell. 
     
     
         45 . The method of  claim 42 , wherein said antibody is detectably labeled. 
     
     
         46 . A method of diagnosing the presence of a tumor in a mammal, said method comprising determining the level of expression of a gene encoding a TAT211 polypeptide in a test sample of tissue cells obtained from said mammal and in a control sample of known normal cells of the same tissue origin, wherein a higher level of expression of said TAT211 polypeptide in the test sample, as compared to the control sample, is indicative of the presence of tumor in the mammal from which the test sample was obtained. 
     
     
         47 . The method of  claim 46 , wherein the step of determining the level of expression of a gene encoding said polypeptide comprises employing an oligonucleotide in an in situ hybridization or RT-PCR analysis. 
     
     
         48 . The method of  claim 46 , wherein the step determining the level of expression of a gene encoding said protein comprises employing an antibody in an immunohistochemistry or Western blot analysis. 
     
     
         49 . The method of  claim 46 , wherein said tumor is an ovarian or lung tumor. 
     
     
         50 . The method of  claim 46 , wherein said TAT211 polypeptide comprises the amino acid sequence of SEQ ID NO:2 or an extracellular domain thereof. 
     
     
         51 . A method of diagnosing the presence of a tumor in a mammal, said method comprising contacting a test sample of tissue cells obtained from said mammal with an antibody of  claim 1  and detecting the formation of a complex between said antibody and a TAT211 protein in the test sample, wherein the formation of a complex is indicative of the presence of a tumor in said mammal. 
     
     
         52 . The method of  claim 51 , wherein said test sample of tissue cells is obtained from an individual suspected of having a cancerous tumor. 
     
     
         53 . The method of  claim 52 , wherein said cancerous tumor is an ovarian or lung tumor. 
     
     
         54 . The method of  claim 51 , wherein said TAT211 protein comprises the amino acid sequence of SEQ ID NO:2 or an extracellular domain thereof.