2001 Fiscal Year Final Research Report Summary
A Specific Study for Clinical Application of a New Tumor-associated Antigen, MK-1,
| Project/Area Number |
12672261
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Fukuoka University |
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Principal Investigator |
KUROKI Masahide School of Medicine, Fukuoka University Professor, 医学部, 教授 (40122692)
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| Co-Investigator(Kenkyū-buntansha) |
黒木 求 福岡大学, 医学部, 講師 (10131822)
荒川 文子 福岡大学, 医学部, 助手 (50212618)
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| Project Period (FY) |
2000 – 2001
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| Keywords | tumor-associated antigen / tumor marker / EIA / MK-1 / 17-1A / GA733-2 / monoclonal antibody / FU-MK-1 |
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| Research Abstract |
The tumor-associated MK-1 antigen, recognized by MAb FU-MK-1, is widely expressed on almost all carcinomas. Recent molecular characterization confirmed that MK-1 is a transmembrane glycoprotein with molecular mass of 40 kDa and is encoded by the GA733-2 gene. In this study, we investigated if MK-1 could be a useful tumor marker and also could be a useful target antigen for cancer immunotherapy.
First, we produced a recombinant MK-1 protein in silkworms by the Bombyx mori nuclear polyhedorosis virus expression system, and newly generated anti-MK-1 MAbs using the recombinant MK-1 protein as immunogen. Then, we established an EIA system for determination of MK-1. The assay range was 2 - 1,000 ng/ml. Serum samples of 236 patients with malignant disease as well as of 20 healthy individuals were tested with the MK-1 EIA. The sensitivity of MK-1 for malignant disease was 10.2% (24/236) and for all healthy individuals the MK-1 concentrations were less than the detection limit This result suggests that MK-1 might be useful for in cases without any elevation of other established tumor markers.
Second, we constructed a recombinant fusion protein of the bacterial superantigen staphylococcal enterotoxin J (SEA) and the single-chain variable fragment (scFv) of the FU-MK-1 antibody. SEA is an extremely potent activator of T lymphocytes when presented on MHC class II molecules. The resulting fusion protein (SEA/FUscFv) was produced by a bacterial expression system and characterized for the antitumor activity. The SEA/FUscFv fusion protein introduced a specific cytotoxicity of T-LAK cells to the tumor cells and consequently suppressed the tumor growth in a SCID mouse xenograft model. This result indicates that the SEA/FUscFv fusion protein may serve as a potentially useful immunotherapeutic reagent for human MK-1 -expressing tumors.
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Research Products
(19 results)
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[Publications] Tomita, T., Arakawa, F., Yamamoto, T., Kuwahara, M., Watanabe, R., Iwasaki H., Kikuchi, M., Kuroki, Ma: "Molecular identification of a human carcinoma-associated glycoprotein antigen recognized by mouse monoclonal antibody FU-MK-1"Jpn.J.Cancer Res.. 91. 231-238 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Tomita, Y., Arakawa, F., Liao, S., Khare, P.D., Kuroki, Mo., Yamamoto, T., Ariyoshi, A., Kuroki, Ma.: "Carcinoma-associated antigens MK-1 and CEA in urological cancers"Anticancer Res.. 20. 793-797 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Sato, N., Saga, T., Sakahara, H., Nakamoto, Y., Zhao, S.J., Kuroki, Ma., Iida, Y., Endo, K., Konishi, J.: "Avidin chase can reduce myelotoxicity associated with radioimmunotherapy of experimental liver micrometastases in mice"Jpn.J.Cancer Res.. 91. 622-628 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Kuroki, Ma., Arakawa, F., Khare, P.D., Kuroki, Mo., Liao, S., Matsumoto, H., Abe, H., Imakiire, T.: "Specific targeting strategies of cancer gene therapy using a single-chain variable fragment (scFv) with a high affinity for CEA"Anticancer Res.. 20. 4067-4071 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Khare, P.D., Liao, S., Kuroki, Mo., Hirose, Y., Arakawa, F., Nakamura, K., Tomita, Y., Kuroki, Ma.: "Specifically targeted killing CEA-expressing cells by a retroviral vector displaying scFv antibody to CEA and carrying the gene for iNOS"Cancer Res.. 61. 370-375 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Saga, T., Sakahara, H., Nakamoto, Y., Sato, N., Ishimori, T., Sasai, K., Kuroki, Ma., Konishi, J.: "Enhancement of the therapeutic outcome of radio-immunotherapy by combination with whole-body mild hyperthermia"Eur.J.Cancer. 37. 1429-1434 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Khare, P.D., Liao, S., Kuroki, M., Arakawa, F., Kuroki, Ma.: "2nd Congress of the Federati on of Immunological Societies of Asia-Oceania (FIMSA)"Sirisinha, S.C.Chaiyaroj and P.Tapchaisri, eds.), Monduzzi Editore, Bologna (Italy). 160 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Tomita,T., Arakawa,F., Yamamoto,T., Kuwahara,M., Watanabe,R., Iwasaki,H., Kikuchi,M., Kuroki,Ma.: "Molecular identification of a human carcinoma-associated glycoproteih antigen recognized by mouse monoclonal antibody FU-MK-1"Jpn. J. Cancer Res.. 91(2). 231-238 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Watanabe,N., Oriuchi,N., Inoue,T., Kuroki,Ma., Matsuoka,Y., Tanaka,S., Murata,H., Kim,E.E., Sasaki,Y.: "CaNa_2EDTA for improvement of radioimmunodetection and radioimmunotherapy with <111>^ln and <90>^Yttrium-DTPA-anti-CEA MAbs in nude micebearing human colorectal cancer"J. Nucl. Med.. 41(2). 337-344 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tomita,Y., Arakawa,F., Liao,S., Khare,P.D., Kuroki,Mo., Yamamoto,T., Ariyoshi,A., Kuroki,Ma.: "Carcinoma-associated antigens MK-1 and CEA in urological cancers"Anticancer Res.. 20(2). 793-797 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sato,N., Saga,T., Sakahara,H., Nakamoto,Y., Zhao,S.J., Kuroki,Ma., Iida,Y., Endo,K., Konishi,J.: "Avidin chase can reduce myelotoxicity associated with radioimmunotherapy of experimental liver micrometastases in mice"Jpn. J. Cancer Res.. 91(6). 622-628 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kuroki,Mo., Arakawa,F., Khare,P.D., Kuroki,Mo., Liao,S., Matsumoto,H., Abe,H., Imakiire,T.: "Specific targeting strategies of cancer gene therapy using a single-chain variable fragment (scFv) with a high affinity for CEA"Anticancer Res.. 20(6). 4067-4071 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Oikawa,S., Sugiyama,M., Kuroki,Mo., Kuroki,Ma., Nakazato,H.: "Extracellular N-domain alone is sufficient for specific heterophlic adhesion between members of carcinoembryonic antigen family, CD66b and CD66c"Biochem. Biophys. Res. Commun.. 278(3). 564-568 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Khare,P.D., Liao,S., Kuroki,Mo., Hirose,Y., Arakawa F., Nakamura,K., Tomita,Y., Kuroki,Ma.: "Specifically targeted killing carcinoembryonic antigen (CEA)-expressing cells by a retrbviral vector displaying single chain variable fragmented (scFv) antibody to CEA and carrying the gene for inducible nitric oxide synthase (iNOS)"Cancer Res.. 61(1). 370-375 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Liao,S., Khare,P.D., Kuroki,Mo., Arakawa,F., Tomita,Y., Kuroki,Ma.: "Targeting of lymphokine-activated killer activity to CEA-expressing tumor cells with a recombinant fusion protein of IL-2 and anti-CEA scFv antibody"Antiancer Res.. 21(3). 1673-1680 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Saga T., Sakahara H., Nakamoto Y., Sato N., Ishimori T., Mamede M., Kobayashi H., Masunaga S., Sasai K., Kuroki Ma., Konishi J.: "Enhancement of the therapeutic outcome of radio-immunotherapy by combination with whole-body mild hyperthermia"Eur. J. Cancer. 37(11). 1429-1434 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kondo,Y., Hinoda,Y., Akashi,H., Sakamoto,H., Itoh,F., Hirata,K., Kuroki,Ma., Imai,K.: "Measurement of circulating biliary glycoprotein (CD66a) in liver diseases"J. Gastroenterol.. 36(7). 470-475 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Jirsa,M., Muchova,L., Draberova,L., Draber,P., Smid,F., Kuroki,Ma., Marecek Z., Groen,A.K.: "Carcinoembryonic antigen-related cell adhesion molecule 1 is the 85-kDa pronase-resistant biliary glycoprotein in the cholesterol crystallization promoting low density protein-lipid complex"Hepatology. 34(6). 1075-1082 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Khare,P.D., Liao,S., Kuroki,M., Arakawa,F., Kuroki,Ma.: "Specific gene therapy of CEA-expressing tumor cells using reconstructed retrovirus"In : 2nd Congress of the Federation of Immunolo-gical Societies of Asia-Oceania (S. Sirisinha, S. C. Chaiyaroj and P. Tapchaisri, eds.), Monduzzi Editore, Bologna (Italy). 51-55 (2000)
Description
「研究成果報告書概要(欧文)」より
