Genetic Products Differentially Expressed In Tumors And The Use Thereof
The present technology relates to the identification of genetic products expressed in association with tumors and to coding nucleic acids for the expressed products. An embodiment of the present technology also relates to the therapy and diagnosis of disease in which the genetic products are aberrantly expressed in association with tumors, proteins, polypeptides and peptides which are expressed in association with tumors, and to the nucleic acids coding for the polypeptides, peptides and proteins.
1 . A method of treating cancer comprising
administering to a patient having said cancer a purified antibody or an antigen binding fragment thereof that specifically binds to a deglycosylated epitope of a tumor-associated antigen that is expressed or abnormally expressed on a cell, said tumor-associated antigen being selected from the group consisting of: (a) a tumor-associated antigen comprising the amino acid sequence of SEQ ID NO: 16; and (b) a tumor-associated antigen encoded by a nucleic acid comprising SEQ ID NO: 7, wherein said cancer is selected from the group consisting of lung cancer, pancreatic cancer, esophageal cancer, stomach cancer, gastric carcinoma, liver cancer, ear nose throat (ENT) cancer.
2 . The method of claim 1 , wherein the purified antibody is a monoclonal, chimeric, or humanized antibody.
3 . The method of claim 1 , wherein a conjugate between the purified antibody or an antigen binding fragment thereof and at least one therapeutic agent.
4 . The method of claim 3 , wherein said therapeutic agent is a toxin.
5 . The method of claim 3 , wherein said therapeutic agent is selected from the group consisting essentially of aminoglutethimide, azathioprine, bleomycin sulfate, busulfan, carmustine, chlorambucil, cisplatin, cyclophosphamide, cyclosporine, cytarabidine, dacarbazine, dactinomycin, daunorubin, doxorubicin, taxol, etoposide, fluorouracil, interferon-α, lomustine, mercaptopurine, methotrexate, mitotane, procarbazine hydrochloride, thioguanine, vinblastine sulfate, and vincristine sulfate.
6 . The method of claim 1 , wherein the purified antibody or antigen binding fragment and a pharmaceutically compatible carrier are comprised in a pharmaceutical composition.
7 . The method of claim 6 , wherein the purified antibody causes induction of cell death, reduction in cell growth, cell membrane damage, or secretion of cytokines.
8 . The method of claim 7 , wherein said purified antibody is a complement-activating antibody, a monoclonal antibody, a chimeric antibody, or a humanized antibody.
9 . The method of claim 7 , wherein said purified antibody is coupled to a therapeutic agent.
10 . The method of claim 9 , wherein said therapeutic agent is a toxin.
11 . The method of claim 9 , wherein said therapeutic agent is selected from the group consisting essentially of aminoglutethimide, azathioprine, bleomycin sulfate, busulfan, carmustine, chlorambucil, cisplatin, cyclophosphamide, cyclosporine, cytarabidine, dacarbazine, dactinomycin, daunorubin, doxorubicin, taxol, etoposide, fluorouracil, interferon-α, lomustine, mercaptopurine, methotrexate, mitotane, procarbazine hydrochloride, thioguanine, vinblastine sulfate and vincristine sulfate.
12 . The method of claim 1 , wherein the antibody or antigen binding fragment thereof does not bind a glycosylated form of the tumor antigen of SEQ ID NO:16.
13 . The method of claim 1 , wherein the deglycosylated epitope of SEQ ID NO:16 comprises at least at one amino acid selected from the group consisting of amino acids at position 37, 38, 45, 116, 141, 145, 153, 205, 234, and 237.
14 . The method of claim 1 , wherein the deglycosylated epitope of SEQ ID NO:16 comprises amino acid position 37.
15 . The method of claim 1 , wherein the purified antibody is obtained by immunization with a peptide against SEQ ID NO:113.