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Significance of a new tumor-associated antigen, MK-1, for diagnosis and therapy of cancer

Research Project

Project/Area Number 16590468
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionFukuoka University

Principal Investigator

KUROKI Masahide  Fukuoka University, Faculty of Medicine, Professor, 医学部, 教授 (40122692)

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)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
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)
Keywordstumor-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.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (26 results)

All 2005 2004

All Journal Article (25 results) Book (1 results)

  • [Journal Article] Preparation of human IgG and 1gM monoclonal antibodies for MK-l/Ep-CAM by using human immunoglobulin gene-transferred mouse and gene cloning of their variable recions2005

    • Author(s)
      Kuroki M, Yamada H, Shibaguchi H, Hachimine K, Hirose Y, et a!.
    • Journal Title

      Anticancer Research 25・6

      Pages: 3733-3739

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Targeting of cancer gene therapy with antibodies or their genes against tumor-associated antigens2005

    • Author(s)
      Kuroki M, Shibaguchi H, Kuroki M, Kinugasa T, Hachimine K, et a!.
    • Journal Title

      Gene Therapy and Molecular Biology 9・A

      Pages: 107-112

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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 M, Yamada H, Shibaguchi H, Hachimine K, Hirose Y, et al.
    • Journal Title

      Anticancer Research 25-6

      Pages: 3733-3739

    • NAID

      40015524500

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Targeting of cancer gene therapy with antibodies or their genes against tumor-associated antigens2005

    • Author(s)
      Kuroki M, Shibaguchi H, Kuroki M, Kinugasa T, Hachimine K, et al.
    • Journal Title

      Gene Therapy and Molecular Biology 9-A

      Pages: 107-112

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 癌関連抗原MK-1に特異的なヒトモノクローナル抗体の作製2005

    • Author(s)
      黒木 求, 山田博美, 芝口浩智, ほか
    • Journal Title

      日本分子腫瘍マーカー研究会誌 20-1

      Pages: 44-45

    • NAID

      130004436335

    • Related Report
      2005 Annual Research Report
  • [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.
    • Journal Title

      Anticancer Research 25-6A

      Pages: 3733-3739

    • NAID

      40015524500

    • Related Report
      2005 Annual Research Report
  • [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.
    • Journal Title

      Journal of Heart and Lung Transplantation 24・10

      Pages: 1557-1564

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 癌の抗体療法2005

    • Author(s)
      黒木 求, 黒木政秀
    • Journal Title

      Biotherapy 19・2

      Pages: 125-132

    • Related Report
      2005 Annual Research Report
  • [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.
    • Journal Title

      Gene Therapy and Molecular Biology 9-A

      Pages: 107-112

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Re-targeting of cytotoxic T lymphocytes and/or natural killer cells to CEA-expressing tumor cells with anti-CEA antibody activity2005

    • Author(s)
      Kuroki, Ma., Hachimine, K., Huang J., Shibaguchi, H., Kinugasa, T., et al.
    • Journal Title

      Anticancer Research 25・6A

      Pages: 3725-3732

    • NAID

      40015524514

    • Related Report
      2005 Annual Research Report
  • [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.
    • Journal Title

      Analytical Sciences 21・1

      Pages: 215-218

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Strategies to endow cytotoxic T lymphocytes or natural killer cells with antibody activity against carcinoembryonic antigen2004

    • Author(s)
      Kuroki, M, Kuroki M, Shibaguchi H, Badran A, Hachimine K, et a!.
    • Journal Title

      Tumor Biology 25・4

      Pages: 208-216

    • NAID

      40015524501

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] KMマウスによるヒト抗体作製-抗CEA抗体を中心として-2004

    • Author(s)
      黒木政秀, 黒木 求, 芝口浩智
    • Journal Title

      分子細胞治療 3・4

      Pages: 435-441

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Generation and targeting of human tumor-specific Tcl and Thl cells ttansduced with a lentivirus containing a chimeric immunoglobulin T-cell receptor2004

    • Author(s)
      Gyobu H, Tsuji T, Suzuki Y, Ohkuri T, Chamoto K, Kuroki M, et a!.
    • Journal Title

      Cancer Research 64・4

      Pages: 1490-1495

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Generation, immunologic characterization and antitumor effects of human monoclonal antibodies for carcinoembryonic antigen2004

    • Author(s)
      Imakiire T, Kuroki M, Shibaguchi H, Abe H, Yarnauchi Y, Ueno A, et al.
    • Journal Title

      International Journal of Cancer 108・4

      Pages: 564-570

    • NAID

      40015524502

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Strategies to endow cytotoxic T lymphocytes or natural killer cells with antibody activity against carcinoembryonic antigen2004

    • Author(s)
      Kuroki, M, Kuroki M, Shibaguchi H, Badran A, Hachimine K, et al.
    • Journal Title

      Tumor Biology 25-4

      Pages: 208-216

    • NAID

      40015524501

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Preparation of human monoclonal antibodies by using the KM mouse2004

    • Author(s)
      Kuorki M, Kuroki M, Shibaguchi H
    • Journal Title

      Cellular and Molecular Medicine 3-4

      Pages: 435-441

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Generation and targeting of human tumor-specific Tc1 and Th1 cells transduced with a lentivirus containing a chimeric immunoglobulin T-cell receptor2004

    • Author(s)
      Gyobu H, Tsuji T, Suzuki Y, Ohkuri T, Chamoto K, Kuroki M, et al.
    • Journal Title

      Cancer Research 64-4

      Pages: 1490-1495

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Generation, immunologic characterization and antitumor effects of human monoclonal antibodies for carcinoembryonic antigen2004

    • Author(s)
      Imakiire T, Kuroki M, Shibaguchi H, Abe H, Yamauchi Y, Ueno A, et al.
    • Journal Title

      International Journal of Cancer 108-4

      Pages: 564-570

    • NAID

      40015524502

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene therapy in cancer via use of a retrovector having a tumor specificity and expressing inducble nitric oxide synthase.2004

    • Author(s)
      Kuroki M
    • Journal Title

      Methods in Molecular Biology, Nitric Oxide Protocols, (Humana Press, Totowa (USA)) Vol.279

      Pages: 201-211

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Generation, immunologic characterization and antitumor effects of human monoclonal antibodies for carcinoembryonic antigen2004

    • Author(s)
      Imakiire, T., Kuroki, Mo., Shibaguchi, H., Abe, H., et al.
    • Journal Title

      International Journal of Cancer 108・4

      Pages: 564-570

    • NAID

      40015524502

    • Related Report
      2004 Annual Research Report
  • [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.
    • Journal Title

      Cancer Research 64・4

      Pages: 1490-1495

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 癌胎児性抗原(CEA)に対する特異的ヒト単鎖抗体45kHscFvの作製とその性状解析2004

    • Author(s)
      芝口浩智, 黒木 求, 廣瀬由美子, ほか
    • Journal Title

      Cancer Science 95・Suppl.

      Pages: 310-310

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CEAおよびMK-1に対するヒトモノクローナル抗体の作製と応用2004

    • Author(s)
      黒木 求, 芝口浩智, 黒木政秀
    • Journal Title

      Cancer Science 95・Suppl.

      Pages: 392-392

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cloning and sequencing of variable region cDNAs of a novel human monoclonal antibody carcinoembryonic antigen and generation of a single chain variable fragmented antibo2004

    • Author(s)
      Shibaguchi, H., Kuroki, Ma., Kuroki, Mo., Badran, A., et al.
    • Journal Title

      Anticancer Research 24・5C

      Pages: 3355-3360

    • Related Report
      2004 Annual Research Report
  • [Book] Methods in Molecular Biology2004

    • Author(s)
      Kuroki M
    • Total Pages
      246
    • Publisher
      Humana Press (Totowa, NJ, USA)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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