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

Creation of a new drug with a bispecific antibody against mesenchymal tissue

Research Project

Project/Area Number 24680093
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Clinical oncology
Research Institution独立行政法人医薬基盤研究所

Principal Investigator

KAMADA Haruhiko  独立行政法人医薬基盤研究所, 創薬基盤研究部, サブプロジェクトリーダー (00324509)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥26,910,000 (Direct Cost: ¥20,700,000、Indirect Cost: ¥6,210,000)
Fiscal Year 2014: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2013: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2012: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Keywords分子標的治療 / 二重特異性抗体 / 乳がん / CD3 / EphA10 / 抗体 / プロテオミクス
Outline of Final Research Achievements

In our efforts to develop a new bispecific monoclonal antibody drug against breast cancer, we attempted to generate a tandem single-chain variable fragment (taFv) targeting both the T-cell CD3 antigen and Ephrin receptor A10 (EphA10), which were previously identified as breast cancer novel biomarker proteins. We constructed the taFv (EphA10/CD3) expression vector that contain two single chain Fv (scFv) joined by linker. The taFv was expressed transiently and verified for identity by Western blot analysis. By flow cytometry analysis, each monomer and dimer bound both antigens EphA10 and CD3. The taFvs showed highly cytotoxicity specifically against EphA10 over-expression cancer cell line. Most notably, the cytotoxicity of taFv dimer was higher than taFv monomer at low Effector/Target ratio and low concentration. This taFv (EphA10/CD3) could induce EphA10 specific cytotoxicity. And also, this BsAb showed the therapeutic effects against EphA10-expressing tumor cells in vivo.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (13 results)

All 2015 2014 2013 2012

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (9 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Generation and characterization of a bispecific diabody targeting both EPH receptor A10 and CD32015

    • Author(s)
      Haruhiko Kamada, Shintaro Taki, Kazuya Nagano, Masaki Inoue, Daisuke Ando, Yohei Mukai, Kazuma Higashisaka, Yasuo Yoshioka, Yasuo Tsutsumi, Shin-ichi Tsunoda
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 456 Issue: 4 Pages: 908-912

    • DOI

      10.1016/j.bbrc.2014.12.030

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of Eph receptor A10 is correlated with lymph node metastasis and stage progression in breast cancer patients.2013

    • Author(s)
      Nagano K, Kanasaki S, Yamashita T, Maeda Y, Inoue M, Higashisaka K, Yoshioka Y, Abe Y, Mukai Y, Kamada H, Tsutsumi Y, Tsunoda S.
    • Journal Title

      Cancer Med.

      Volume: 2 Pages: 972-977

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Optimization of bispecific antibody targeting CD3 and EphA10 as a bio-drug candidate against breast cancer.2014

    • Author(s)
      Taki S., Kamada H., Inoue M., Nagano K., Mukai Y., Tsutsumi Y., Tsunoda S.
    • Organizer
      The 19th JFCR-ISCC
    • Place of Presentation
      Tokyo (Tokyo)
    • Year and Date
      2014-12-10 – 2014-12-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 抗腫瘍活性の向上にむけたBispecific抗体の最適化.2014

    • Author(s)
      瀧慎太郎, 鎌田春彦, 長野一也, 向 洋平, 堤 康央, 角田慎一
    • Organizer
      第13回次世代を担う若手ファーマ・バイオフォーラム2014
    • Place of Presentation
      富山(富山)
    • Year and Date
      2014-09-20 – 2014-09-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 難治性乳がんをターゲットとする新規Bispecific抗体(EphA10/CD3)の創製.2014

    • Author(s)
      瀧慎太郎, 鎌田春彦, 井上雅己, 長野一也, 向 洋平, 堤 康央, 角田慎一
    • Organizer
      第18回日本がん分子標的治療学会学術集会.
    • Place of Presentation
      仙台(宮城)
    • Year and Date
      2014-06-25 – 2014-06-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] EphA10とCD3を認識する新規Bispecific抗体(EphA10/CD3)の創製とT細胞活性化に関する考察.2014

    • Author(s)
      瀧慎太郎, 鎌田春彦, 井上雅己, 長野一也, 向 洋平, 堤 康央, 角田慎一
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] EphA10を創薬ターゲットとしてtandem scFV型Bispecific抗体の新規乳がん治療法の開発2014

    • Author(s)
      鎌田 春彦
    • Organizer
      新学術領域「がん研究分野の特性等を踏まえた研究支援活動」公開シンポジウム.
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 乳がん関連たんぱく質EphA10を標的としたtandem scFv型bispecific抗体の開発2013

    • Author(s)
      瀧慎太郎, 鎌田春彦, 井上雅己, 前田祐香, 長野一也, 向 洋平, 堤 康央, 角田慎一
    • Organizer
      第29回日本DDS学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Eph receptor A10を標的とした新規乳がん治療薬開発の試み2012

    • Author(s)
      前田祐香、鎌田春彦, 他
    • Organizer
      第62回日本薬学会近畿支部総会・大会
    • Place of Presentation
      西宮(兵庫)
    • Year and Date
      2012-10-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] Evaluation of Eph receptor A10 as a novel drug target for breast cancer.2012

    • Author(s)
      前田祐香、鎌田春彦, 他
    • Organizer
      第71回日本癌学会学術集会
    • Place of Presentation
      札幌(北海道)
    • Year and Date
      2012-09-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] 新規乳がん分子標的治療薬の開発に向けたEph receptor A10に対するモノクローナル抗体の作2012

    • Author(s)
      前田祐香、鎌田春彦, 他
    • Organizer
      第28回日本DDS学会学術集会
    • Place of Presentation
      札幌(北海道)
    • Year and Date
      2012-07-04
    • Related Report
      2012 Annual Research Report
  • [Book] 臨床プロテオミクス~バイオマーカー探索から個別化医療へ2012

    • Author(s)
      鎌田春彦, ほか(共著)
    • Publisher
      金原出版株式会社
    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] 二重特異性抗体及び医薬組成物2012

    • Inventor(s)
      鎌田春彦、角田慎一
    • Industrial Property Rights Holder
      医薬基盤研究所
    • Industrial Property Number
      2013-033677
    • Filing Date
      2012-02-22
    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi