2005 Fiscal Year Final Research Report Summary
Significance of a new tumor-associated antigen, MK-1, for diagnosis and therapy of cancer
| Project/Area Number |
16590468
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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 Fukuoka University, Faculty of Medicine, Professor, 医学部, 教授 (40122692)
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| Co-Investigator(Kenkyū-buntansha) |
KUROKI Motomu Fukuoka University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (10131822)
SHIBAGUCHI Hirotomo Fukuoka University, Faculty of Medicine, Research Associate, 医学部, 助手 (60295061)
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| Project Period (FY) |
2004 – 2005
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| Keywords | tumor-associated antigen / MK-1 / 17-1A / Ep-CAM / immunoassay / human monoclonal antibody / CDC / ADCC |
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| Research Abstract |
For antibody-based therapy of cancer, monoclonal antibodies (mAbs) of human origin is superior to mouse, mouse/human chimeric or humanized mAbs, because of its minimum immunogenicity to human and its efficient collaboration with human effector cells. In the present study, we prepared human mAbs against a pan-carcinoma antigen, MK-1 (Ep-CAM), using a genetically engineered mouse (KM mouse^<TM>) that contains the human immunoglobulin genes. Spleen cells from KM mice immunized with recombinant MK-1 were fused with the P3-U1 mouse myeloma cells. Of 44 anti-MK-1 clones analyzed, two were of IgG4 and the others of IgM clones. Although the two IgG4 clones were suggested to recognize the same antigenic determinant or two closely located determinants, their Vk regions were encoded by different light-chain genes while their VH sequences were identical. The two IgG4 and one of the IgM clones tested revealed antibody-dependent cell-mediate cytotoxicity and complement-dependent cytotoxicity, respectively, against MK-1-expressing cells in vitro, suggesting that these fully human mAbs produced against MK-1 and their V-region genes, which are applicable for preparation of engineered antibody fragments, may be useful for antibody-based therapy of cancer.
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