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 |
Section | 一般 |
Research Field |
Laboratory medicine
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Research Institution | Fukuoka University |
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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Project Status |
Completed (Fiscal Year 2005)
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Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Keywords | tumor-associated antigen / MK-1 / 17-1A / Ep-CAM / immunoassay / human monoclonal antibody / CDC / ADCC |
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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Report
(3 results)
Research Products
(26 results)
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[Journal Article] Preparation of human IgG and IgM monoclonal antibodies for MK-1/Ep-CAM by using human immunoglobulin gene-transferred mouse and gene cloning of their variable regions2005
Author(s)
Kuroki, Mo., Yamada, H., Shibaguchi, H., Hachimine, K., Hirose, Y., et al.
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Journal Title
Anticancer Research 25-6A
Pages: 3733-3739
NAID
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[Journal Article] Prevention of acute lung allograft rejection in rat by the Janus kinase 3 inhibitor. tyrphostin AG4902005
Author(s)
Higuchi, T., Shiraishi, T., Hirayama, S., Shibaguchi, H., Kuroki, Mo., et al.
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Journal Title
Journal of Heart and Lung Transplantation 24・10
Pages: 1557-1564
Related Report
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[Journal Article] Targeting of cancer gene therapy with antibodies or their genes against tumor-associated antigens2005
Author(s)
Kuroki, Ma., Shibaguchi, H., Kuroki, Mo., Kinugasa, T., Hachimine, K., et al.
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Journal Title
Gene Therapy and Molecular Biology 9-A
Pages: 107-112
Related Report
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[Journal Article] Interaction analysis of CEA with its monoclonal antibody immobilized on a gold surface using fourier transform infrared reflection-absorption spectroscopy (FT-IR RAS)2005
Author(s)
Ohtsuka, K., Kuroki, Ma., Nojima, T., Waki, M., Takenaka, S., et al.
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Journal Title
Analytical Sciences 21・1
Pages: 215-218
Related Report
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[Journal Article] Generation and targeting of human tumor-specific Tc1 cells transduced with a lentivirus containing a chimeric immunoglobulin T cell receptor2004
Author(s)
Gyobu, H., Tsuji, T., Suzuki, Y., Ohkuri, T., Chamoto, K., et al.
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Journal Title
Cancer Research 64・4
Pages: 1490-1495
Related Report
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