Neoplasm specific antibodies and uses thereof

Abstract

The present invention features polypeptides, such as antibodies, and their use in the treatment and diagnosis of neoplasms.

1 . A purified polypeptide that induces apoptosis of a neoplastic cell to which it binds, but does not induce apoptosis of a non-neoplastic cell, wherein said polypeptide specifically binds to at least one of HT-29 (ATCC Accession No. HTB-38; DSMZ Accession No. ACC 299), CACO-2 (ATCC Accession No. HBT-37; DSMZ Accession No. ACC 169), COLO-320 (DSMZ Accession No. ACC 144), COLO-206F (DSMZ Accession No. ACC 21), ASPC-1 (ATCC Accession No. CRL-1682), or BXPC-3 (ATCC Accession No. CRL-1687) cells and not to non-neoplastic cells. 
     
     
         2 . The purified polypeptide of  claim 1 , wherein said polypeptide binds to ASPC-1 (ATCC Accession No. CRL-1682) and BXPC-3 (ATCC Accession No. CRL-1687) cells and not to non-neoplastic cells, and wherein said neoplastic cell is a stomach adenocarcinoma, colorectal adenocarcinoma, squamous cell lung carcinoma, lung adenocarcinoma, squamous cell carcinoma of the esophagus, adenocarcinoma of the pancreas, adenocarcinoma of the prostate, ductal carcinoma of the breast, lobular carcinoma of the breast, adenocarcinoma of the ovary, or adenocarcinoma of the uterus cell. 
     
     
         3 . The purified polypeptide of  claim 1 , wherein said polypeptide binds to HT-29 (ATCC Accession No. HTB-38; DSMZ Accession No. ACC 299), CACO-2 (ATCC Accession No. HBT-37; DSMZ Accession No. ACC 169), COLO-320 (DSMZ Accession No. ACC 144), COLO-206F (DSMZ Accession No. ACC 21), ASPC-1 (ATCC Accession No. CRL-1682), and BXPC-3 (ATCC Accession No. CRL-1687) cells and not to non-neoplastic cells, and wherein said neoplastic cell is a stomach adenocarcinoma, colorectal adenocarcinoma, squamous cell lung carcinoma, lung adenocarcinoma, squamous cell carcinoma of the esophagus, adenocarcinoma of the pancreas, urothel carcinoma of the urinary bladder, renal cell carcinoma of the kidney, adenocarcinoma of the prostate, ductal carcinoma of the breast, lobular carcinoma of the breast, adenocarcinoma of the ovary, or adenocarcinoma of the uterus cell. 
     
     
         4 . The purified polypeptide of  claim 1 , wherein said polypeptide binds to CACO-2 (ATCC Accession No. HBT-37; DSMZ Accession No. ACC 169) and COLO-206F (DSMZ Accession No. ACC 21) cells and not to non-neoplastic cells, and wherein said neoplastic cell is a colorectal adenocarcinoma or adenocarcinoma of the endometrium cell. 
     
     
         5 . A purified polypeptide that induces apoptosis of a neoplastic cell to which it binds, but does not induce apoptosis of a non-neoplastic cell, wherein said polypeptide specifically binds to a stomach adenocarcinoma, colorectal adenocarcinoma, squamous cell lung carcinoma, lung adenocarcinoma, squamous cell carcinoma of the esophagus, adenocarcinoma of the pancreas, urothel carcinoma of the urinary bladder, renal cell carcinoma of the kidney, adenocarcinoma of the prostate, ductal carcinoma of the breast, lobular carcinoma of the breast, adenocarcinoma of the ovary, adenocarcinoma of the endometrium, or adenocarcinoma of the uterus cell and not to a non-neoplastic cell. 
     
     
         6 . A purified polypeptide that inhibits cell proliferation when bound to a neoplastic cell, but does not inhibit cell proliferation of a non-neoplastic cell, wherein said polypeptide specifically binds to at least one of HT-29 (ATCC Accession No. HTB-38; DSMZ Accession No. ACC 299), CACO-2 (ATCC Accession No. HBT-37; DSMZ Accession No. ACC 169), COLO-320 (DSMZ Accession No. ACC 144), COLO-206F (DSMZ Accession No. ACC 21), ASPC-1 (ATCC Accession No. CRL-1682), or BXPC-3 (ATCC Accession No. CRL-1687) cells and not to non-neoplastic cells. 
     
     
         7 . The purified polypeptide of  claim 6 , wherein said polypeptide binds to ASPC-1 (ATCC Accession No. CRL-1682) and BXPC-3 (ATCC Accession No. CRL-1687) cells and not to non-neoplastic cells, and wherein said neoplastic cell is a stomach adenocarcinoma, colorectal adenocarcinoma, squamous cell lung carcinoma, lung adenocarcinoma, squamous cell carcinoma of the esophagus, adenocarcinoma of the pancreas, adenocarcinoma of the prostate, ductal carcinoma of the breast, lobular carcinoma of the breast, adenocarcinoma of the ovary, or adenocarcinoma of the uterus cell. 
     
     
         8 . The purified polypeptide of  claim 6 , wherein said polypeptide binds to HT-29 (ATCC Accession No. HTB-38; DSMZ Accession No. ACC 299), CACO-2 (ATCC Accession No. HBT-37; DSMZ Accession No. ACC 169), COLO-320 (DSMZ Accession No. ACC 144). COLO-206F (DSMZ Accession No. ACC 21), ASPC-1 (ATCC Accession No. CRL-1682), and BXPC-3 (ATCC Accession No. CRL-1687) cells and not to non-neoplastic cells, and wherein said neoplastic cell is a stomach adenocarcinoma, colorectal adenocarcinoma, squamous cell lung carcinoma, lung adenocarcinoma, squamous cell carcinoma of the esophagus, adenocarcinoma of the pancreas, urothel carcinoma of the urinary bladder, renal cell carcinoma of the kidney, adenocarcinoma of the prostate, ductal carcinoma of the breast, lobular carcinoma of the breast, adenocarcinoma of the ovary, or adenocarcinoma of the uterus cell. 
     
     
         9 .- 21 . (canceled) 
     
     
         22 . The purified polypeptide of  claim 1 , wherein said polypeptide comprises a sequence that is substantially identical to the amino acid sequence of SEQ ID NO:1. 
     
     
         23 . The purified polypeptide of  claim 1 , wherein said polypeptide comprises a sequence that is substantially identical to the amino acid sequence of SEQ ID NO:3. 
     
     
         24 . The purified polypeptide of  claim 1 , wherein said polypeptide comprises a sequence that is substantially identical to the amino acid sequence of SEQ ID NO:5. 
     
     
         25 . The purified polypeptide of  claim 1 , wherein said polypeptide comprises a sequence that is substantially identical to the amino acid sequence of SEQ ID NO:7. 
     
     
         26 . The purified polypeptide of  claim 1 , wherein said polypeptide comprises a sequence that is substantially identical to the amino acid sequence of SEQ ID NO:9. 
     
     
         27 . The purified polypeptide of  claim 1 , wherein said polypeptide comprises a sequence that is substantially identical to the amino acid sequence of SEQ ID NO:11. 
     
     
         28 . (canceled) 
     
     
         29 . A purified polypeptide comprising amino acid 26-31, 49-51, and 88-95 of SEQ ID NO:1. 
     
     
         30 . (canceled) 
     
     
         31 . A purified polypeptide comprising amino acids 11-18, 36-43, and 82-90 of SEQ ID NO:3. 
     
     
         32 . (canceled) 
     
     
         33 . A purified polypeptide comprising amino acids 26-34, 52-58, and 97-103 of SEQ ID NO:5. 
     
     
         34 . (canceled) 
     
     
         35 . A purified polypeptide comprising amino acids 11-18, 36-43, and 82-100 of SEQ ID NO:7. 
     
     
         36 . (canceled) 
     
     
         37 . A purified polypeptide comprising amino acids 26-34, 51-54, and 91-99 of SEQ ID NO:9. 
     
     
         38 . (canceled) 
     
     
         39 . A purified polypeptide comprising amino acids 16-22, 40-47, and 86-100 of SEQ ID NO:11. 
     
     
         40 . (canceled) 
     
     
         41 . A purified polypeptide comprising amino acid 26-31, 49-51, and 88-95 of SEQ ID NO:1 and amino acids 11-18, 36-43, and 82-90 of SEQ ID NO:3. 
     
     
         42 . (canceled) 
     
     
         43 . A purified polypeptide comprising amino acids 26-34, 52-58, and 97-103 of SEQ ID NO:5 and amino acids 11-18, 36-43, and 82-100 of SEQ ID NO:7. 
     
     
         44 . (canceled) 
     
     
         45 . A purified polypeptide comprising amino acids 26-34, 51-54, and 91-99 of SEQ ID NO:9 and amino acids 16-22, 40-47, and 86-100 of SEQ ID NO:11. 
     
     
         46 . The purified polypeptide of  claim 1 , wherein said polypeptide is a monoclonal antibody. 
     
     
         47 . The purified polypeptide of  claim 46 , wherein said monoclonal antibody is a human monoclonal antibody. 
     
     
         48 - 76 . (canceled) 
     
     
         77 . Use of the purified polypeptide of  claim 1 , in a method of treating a proliferative disorder in a mammal, said method comprising the step of contacting a cell or tissue sample with the purified polypeptide of  claim 1 , wherein binding of said purified polypeptide to said cell or tissue sample results in the induction of apoptosis of said cell or tissue sample. 
     
     
         78 - 83 . (canceled) 
     
     
         84 . Use of the purified polypeptide of  claim 1 , in a method of treating a proliferative disorder in a mammal, said method comprising the step of contacting a cell or tissue sample with the purified polypeptide of  claim 1 , wherein binding of said purified polypeptide to said cell or tissue sample results in a reduction in proliferation of said cell or of a cell in said tissue sample. 
     
     
         85 - 110 . (canceled)