• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Generation and application of fully human antibodies to a new tumor-associated antigen, Ep-CAM

Research Project

Project/Area Number 18590544
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, Faculyt of Medicine, Professor (40122692)

Co-Investigator(Kenkyū-buntansha) KINUGASA Tetsushi  Fukuoka University, Faculty of Medicine, Senior Assistant Professor (90279266)
SHIBAGUCHI Hirotomo  Fukuoka University, Faculty of Medicine, Senior Assistant Professor (60295061)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordscancer / immunology / biotechnology / monoclonal antibody / Ep-CAM / ADCC / CDC
Research Abstract

There are numerous tumor-associated antigens currently used for the diagnosis and treatment of cancer. However, no tumor-associated antigen can always be an exact and complete target molecule, because almost all of them are not absolutely tumor-specific. In the present study, we prepared human mAbs against a pan-carcinoma antigen, Ep-CAM, using a genetically engineered mouse (KM mouse^<TM>) that contains the human immunoglobulin genes. Spleen cells from KM mice immunized with recombinant Ep-CAM were fused with the P3-U1 mouse myeloma cells. Of 44 anti-Ep-CAM clones analyzed, two were of IgG4 and the others of IgM clones. The two IgG4 clones were suggested to recognize the same antigenic determinant or two closely located determinants. The two IgG4 and one of the IgM clones tested revealed antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, respectively, against Ep-CAM-expressing cells in vitro. It is also known that IgG4 hardly binds to the FcγIII receptor, which involves in ADCC by NK cells. In the presence of the IgG4 clone M13-13, however, a slight increase was observed in the cytotoxicity of IL-2-activated PBMC against tumor cells. IgG4 antibodies are able to bind to the FcγI receptor on monocytes and thereby exert ADCC. The ADCC activity observed with M13-13 might be due to activated monocytes. Therefore, we engineered our IgM clone M11-29 to convert it to the IgG1 type using its V-region genes so that it can exhibit both ADCC and CDC to Ep-CAM-expressing tumor cells. The V-region genes obtained were also useful to prepare single chain Fv antibodies to retarget cylotoxic T cells or a retrovector to tumor cells. Taken together, these data suggest that these fully human mAbs produced against Ep-CAM 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)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (44 results)

All 2007 2006 Other

All Journal Article (23 results) (of which Peer Reviewed: 11 results) Presentation (16 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Correlation between lymph node metastasis and expression of VEGF-C,VEGF-D and VEGFR-3 in T1 lung adenocarcinoma2007

    • Author(s)
      Maekawa, S., Iwasaki, A., Enatsu, S., Kawakami, T., Kuroki, Mo., et. al.
    • Journal Title

      Anticancer Res. 27

      Pages: 3755-3741

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Tumor targeting carboxylesterase fused with anti CEA scFv improve the anticancer effect with a less toxic dose of irinotecan2007

    • Author(s)
      Uchino, J., Takayama, K., Harada, A., Sone, T., et. al.
    • Journal Title

      Cancer Gene Ther. 15

      Pages: 94-100

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Sonodynamic therapy of cancer using a novel porphyrin derivative,DCPH-P-Na(I),which is devoid of photosensitivity2007

    • Author(s)
      Hachimine, K., Shibaguchi, H., Kuroki, Mo., Yamada, H., et. al.
    • Journal Title

      Cancer Sci. 98

      Pages: 916-920

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Correlation between lymph node metastasis and expression of TEGF-C, VEGF-D and VEGFR-3 in T1 lung adenocarcinoma2007

    • Author(s)
      Maekawa, S., Iwasaki, A., Enatsu, S., Kawakami, T., Kuroki, Mo., et. al.
    • Journal Title

      Anticancer Res. 27

      Pages: 3755-3741

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Tumor targeting carboxylesterase fused with anti CEA scFv improve the anticancer effect with a less toxic dose of irinotecan2007

    • Author(s)
      Uchino, J., Takayama, K., Harada, A., Sone, T., Harada, T., et. al.
    • Journal Title

      Cancer Gene Ther 15

      Pages: 94-100

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Sonodynamic therapy of cancer using a novel porphyrin derivative, DCPH-P-Na (I), which is devoid of photosensitivity2007

    • Author(s)
      Hachimine, K., Shibaguchi, H., Kuroki, Mo., Yamada, H., et. al.
    • Journal Title

      Cancer Sci. 98

      Pages: 916-920

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Correlation between lymph node metastasis and expression of VEGF-C,VEGF-D and VEGFR-3 in T1 lung adenocarcinoma2007

    • Author(s)
      Maekawa, S., Iwasaki, A., Enatsu, S., Kawakami, T., Kuroki, Mo, et. al.
    • Journal Title

      Anticancer Res 27

      Pages: 3755-3741

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor targeting carboxylesterase fused withanti CEA scFv improve the anticancer effect with a less toxic dose of irinotecan2007

    • Author(s)
      Uchino, J., Takayama, K., Harada, A., Sone, T., Harada, T., et. al.
    • Journal Title

      Cancer Gene Ther 15

      Pages: 94-100

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sonodynamic therapy of cancer using a novel porphyrin derivative,DCPH-PNa(I),which is devoid of photosensitivity2007

    • Author(s)
      Hachimine, K., Shibaguchi, H., Kuroki, Mo., Yamada, H., et. al.
    • Journal Title

      Cancer Sci 98

      Pages: 916-920

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic value of carcinoma-associated antigen MK-1 in urinary bladdercarcinoma2006

    • Author(s)
      EL-Meghawry EL-Kenawy, A., EL-Kott, A.F., et. al.
    • Journal Title

      Int.J.Bio.Markers 21

      Pages: 170-174

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] MK-1 expression in carcinoma of the ampulla of Vater as a predictor of improved prognosis after surgical resection2006

    • Author(s)
      Hamada, Y., Nakayama, Y., Mizoguchi, M., et. al.
    • Journal Title

      Cancer Lett. 243

      Pages: 211-216

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] CEA-targeted selective gene therapy for gastric cancer through FZ33 fiber modified adenovirus vector2006

    • Author(s)
      Tanaka, T., Huang, J., Hirai, S., Kuroki, Mo., et. al.
    • Journal Title

      Clin.Cancer Res. 12

      Pages: 3803-3813

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Possible applications of antibodies or their genes in cancer therapy2006

    • Author(s)
      Kuroki, M., Huang, J., Shibaguchi, H., Zhao, J., et. al.
    • Journal Title

      Anticancer Res. 26

      Pages: 4019-4026

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Antitumor activity of chimeric immunoreceptor gene-modified Tc1 and Th1 cells against autologous CEA-expressing colon cancer cells2006

    • Author(s)
      Sasaki, T., Ikeda, H., Sato, M., Ohkuri, T., Abe, H., et. al.
    • Journal Title

      Cancer Sci. 97

      Pages: 920-927

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Prognostic value of carcinoma-associated antigen MK-1 in urinary bladder carcinoma2006

    • Author(s)
      EL-Meghawry EL-Kenawy, A., EL-Kott, A. F., et. al.
    • Journal Title

      Int. J. Bio. Markers 21

      Pages: 170-174

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] CEA-targeted selective gene therapy for gastric cancer through FZ33 fiber modified adenovirus vector2006

    • Author(s)
      Tanaka, T., Huang, J., Hirai, S., Kuroki, Mo., et. al.
    • Journal Title

      Clin. Cancer Res. 12

      Pages: 3803-3813

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Antitumor activity of chimeric immunoreceptor gene-modified Tc1 and Th1 cells against autologous CEA expressing colon cancer cells2006

    • Author(s)
      Sasaki, T., Ikeda, H., Sato, M., Ohkuri, T., Abe, H., et. al.
    • Journal Title

      Cancer Sci. 97

      Pages: 920-927

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Prognostic value of carcinoma-associated antigen MK-1 in urinary bladder carcinoma2006

    • Author(s)
      EL-Meghawry, EL-Kenawy, A., EL-Kott, A.F.et al.
    • Journal Title

      Int J Biol.Markers 21・3

      Pages: 171-171

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Possible applications of antibodies or their genes in cancer2006

    • Author(s)
      Kuroki, M, Huang, J, Shibaguchi, H, Zhao, J.et al.
    • Journal Title

      Anticancer Res Cancer Res. 26・6

      Pages: 4019-4026

    • Related Report
      2006 Annual Research Report
  • [Journal Article] CEA-targeted slective gene therapy for gastric cancer through FZ33 fiber modified adenovirus vector2006

    • Author(s)
      Tanakja, T, Huang, J, Hirai, S, kuroki, Mo.et al.
    • Journal Title

      Clin.Cancer Res. 12・12

      Pages: 3803-3813

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Antitumor activity of chimeric immunoreceptor gene-modified Tel and Thl cells against autologous CEA-expressing colon cancer cells2006

    • Author(s)
      Sasaki, T, Ikeda, H, Sato, M, Ohkuri, T, Abe, H.et al.
    • Journal Title

      Cancer Sci. 97・9

      Pages: 920-927

    • Related Report
      2006 Annual Research Report
  • [Journal Article] IgG isotype conversion of a novel human anti-carcinoembonic antigen antibody to increase its biological activity2006

    • Author(s)
      Huang, J, Shibaguchi, H, Zhao, J, Luo, N.et al.
    • Journal Title

      Anticancer Res. 26・2

      Pages: 1057-1064

    • Related Report
      2006 Annual Research Report
  • [Journal Article] MK-1 expression in carcinoma of the ampulla of Vater as a predictor of improved prognosis after surgical resection2006

    • Author(s)
      Hamada, Y, Nakayama, Y, Mizoguchi, M, Ikeda, S.et al.
    • Journal Title

      Cancer Lett. 243・2

      Pages: 211-216

    • Related Report
      2006 Annual Research Report
  • [Presentation] HB-EGF or amphiregulin is a promising target for human cancer therapy2007

    • Author(s)
      四元 房典, 八木 裕史, 園田 顕三, 辻岡 筧, 蜂須 賀徹, ほか
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Selective up-regulation of claudin-1 and claudin-2 in colorectal cancer2007

    • Author(s)
      衣笠 哲史, 黒木 求, 芝口 浩智, 田中 俊裕, ほか
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] HB-EGF or amphiregulin is a promising target for human cancer therapy nation and endocytosis2007

    • Author(s)
      Yotsumoto, F., Yagi, H., Sonoda, K., Tsujioka, H., Hachisuga, T., et. al.
    • Organizer
      66th Ann. Meet. of Jpn Cancer Assoc.
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-10-05
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Selective up-regulation of claudin-1 and claudin-2 in colorectal cancer2007

    • Author(s)
      Kinugasa, T., Kuroki, M., Shibaguchi, H., Tanaka, T., et. al.
    • Organizer
      66th Ann. Meet. of Jpn Cancer Assoc.
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-10-05
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Amphiregulin enchances drug-resistance for pancreatic and colon cancers2007

    • Author(s)
      深見 達弥, 八木 裕史, 四元 房典, 沖 英次, 黒木 政秀, ほか
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-04
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Evaluation of Adv-FZ33 mediated gene transduction among anti-CEA Abs with different subclasses of mouse and human IgGs2007

    • Author(s)
      田中 俊裕, 趙 君, 黒木 求, 衣笠 哲史, 芝口 浩智, 加藤 和則, ほか
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-04
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Amphiregulin enhances drug-resistance for pancreatic and colon cancers.2007

    • Author(s)
      Fukami, T., Yagi, H., Yotsumoto, F., Oki, E., Kuroki, M., et. al.
    • Organizer
      66th Ann. Meet. of Jpn Cancer Assoc.
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-10-04
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Evaluation of Adv-FZ33 mediated gene transduction among anti-CEA Abs with different subclasses of mouse and human IgGs2007

    • Author(s)
      Tanaka, T., Zhao, J., Kuroki, M., Kinugasa, T., et. al.
    • Organizer
      66th Ann. Meet. of Jpn Cancer Assoc.
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-10-04
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression patterns of tight junction associated proteins in colon cancer2006

    • Author(s)
      衣笠 哲史, 黒木 求, 芝口 浩智, 山田 博美, ほか
    • Organizer
      第65回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2006-09-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Pleural lavage cytology before and after lung resection in non-small cell Lung cancer patients2006

    • Author(s)
      江夏 総太郎, 吉田 純司, 横瀬 智之, 西村 光世, 西脇 裕, ほか
    • Organizer
      第65回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2006-09-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Correlation between lymph node metastasis and expression of VEGF-C,-D And VEGFR-3 in primary lung adenocarcinomas2006

    • Author(s)
      前川 信一, 岩崎 昭憲, 江夏 総太郎, 衣笠 哲史, 黒木 求, ほか
    • Organizer
      第65回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2006-09-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression patterns of tight junction associated proteins in colon cancer2006

    • Author(s)
      Kinugasa, T., Kuroki, M., Shibaguchi, H., et. al.
    • Organizer
      65th Ann. Meet. of Jpn Cancer Assoc.
    • Place of Presentation
      Yokohama
    • Year and Date
      2006-09-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Pleural lavage cytology before and after lung resection in non-small cell Lung cancer patients2006

    • Author(s)
      Enatsu, S., Yoshida, J., Yokose, T., Nishimura, M., Nishiwaki, Y., et. al.
    • Organizer
      65th Ann. Meet. of Jpn Cancer Assoc.
    • Place of Presentation
      Yokohama
    • Year and Date
      2006-09-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Correlation between lymph node metastasis and expression of VEGF-C,-D And VEGFR-3 in primary lung adenocarcinomas2006

    • Author(s)
      Maekawa, S., Iwasaki, A., Enatsu, S., Kinugasa, T., Kuroki, M., et. al.
    • Organizer
      65th Ann. Meet. of Jpn Cancer Assoc.
    • Place of Presentation
      Yokohama
    • Year and Date
      2006-09-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] IgG isotype conversion of a novel anti-carcinoembryonic antigen antibody to increase its biological activity2006

    • Author(s)
      芝口 浩智, 黒木 求, 衣笠 哲史, 廣瀬 由美子, 山田 博美, ほか
    • Organizer
      第65回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2006-09-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] IgG isotype conversion of a novel anti-carcinoembryonic antigen antibody to increase its biological activity2006

    • Author(s)
      Shibaguchi, H., Kuroki, M., Kinugasa, T., Hirose, Y., Yamada, H., et. al.
    • Organizer
      65th Ann. Meet. of Jpn Cancer Assoc.
    • Place of Presentation
      Yokohama
    • Year and Date
      2006-09-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Recent Developments in Gene Therapy2007

    • Author(s)
      Tanaka, T., Hamada, H., Kuroki, Mo., Kato, K., et. al.
    • Total Pages
      367
    • Publisher
      Transworld Research Network
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Recent Developmentsin Gene Therapy(J.Xiang, ed.)2007

    • Author(s)
      Tanaka, T., Hamada, H., Kuroki, Mo., Kato, K., Kinugasa, T., et. al.
    • Total Pages
      367
    • Publisher
      Tlransworld Research Network
    • Related Report
      2007 Annual Research Report
  • [Book] Ransworld Reseaech Network

    • Author(s)
      Tanaka, T, Hamada, H, Kuroki, M, Kato K.et al.
    • Publisher
      Ransworld Research Network(in press)
    • Related Report
      2006 Annual Research Report
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.med.fukuoka-u.ac.jp/biochem1/MaK-bunken/kenkyugaiyo.html

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.med.fukuoka-u.ac.jp/biochem1/MaK-bunken/kenkyugaiyo.html

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi