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Challenge to the development of small tetraspecific and tetravalent antibody as innovative cancer therapeutic antibodies

Research Project

Project/Area Number 25640085
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionTokyo University of Agriculture and Technology (2015)
Tohoku University (2013-2014)

Principal Investigator

ASANO Ryutaro  東京農工大学, 工学(系)研究科(研究院), 准教授 (80323103)

Co-Investigator(Kenkyū-buntansha) UMETSU Mitsuo  東北大学, 大学院工学研究科, 教授 (70333846)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords癌 / 蛋白質 / バイオテクノロジー / 生物・生体工学 / 四重特異性四価抗体
Outline of Final Research Achievements

Although small bispecific antibodies are attractive molecules, their decreases in binding valency and in vivo half-life are left as a problem. Multimerization of small antibodies is one strategy to solve these drawbacks. In this study using four kinds of antibody fragments, we tried to develop small tetraspecific and tetravalent cancer therapeutic antibodies to regulate multimeric structure and to enhance therapeutic efficacy. We couldn’t obtain the functional molecules in bacterial expression system; however, we successfully prepared tetraspecific and tetravalent antibodies with high therapeutic effects in mammalian expression system. Further, our results showed that Fc fusion to facilitate their purification causes decreases in their cytotoxic effects.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (17 results)

All 2016 2015 2014 2013

All Journal Article (6 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (11 results) (of which Invited: 5 results)

  • [Journal Article] 二重特異性抗体を用いたがん治療2015

    • Author(s)
      浅野竜太郎, 杉山在生人, 熊谷 泉
    • Journal Title

      細胞

      Volume: 47 Pages: 50-53

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 二重特異性抗体のタンパク質工学を駆使した高機能化2015

    • Author(s)
      浅野竜太郎, 熊谷 泉
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 135 Pages: 851-856

    • NAID

      130005085763

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Glycosylation analysis of an aggregated antibody produced by Chinese hamster ovary cells in bioreactor culture2014

    • Author(s)
      Masayoshi Onitsuka, Akira Kawaguchi, Ryutaro Asano, Izumi Kumagai, Kohsuke Honda, Hisao Ohtake, Takeshi Omasa
    • Journal Title

      Journal of Bioscience and Bioengineering

      Volume: 117 Issue: 5 Pages: 639-644

    • DOI

      10.1016/j.jbiosc.2013.11.001

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rearranging the domain order of a diabody-based IgG-like bispecific antibody enhances its antitumor activity and improves its degradation resistance and pharmacokinetics2014

    • Author(s)
      Ryutaro Asano et al.
    • Journal Title

      MAbs

      Volume: 6 Issue: 5 Pages: 1243-1254

    • DOI

      10.4161/mabs.29445

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Domain order of a bispecific diabody dramatically enhances its antitumor activity beyond structural format conversion: the case of the hEx3 diabody2013

    • Author(s)
      Ryutaro Asano, el al.
    • Journal Title

      Protein Eng. Des. Sel.

      Volume: 26 Issue: 5 Pages: 359-367

    • DOI

      10.1093/protein/gzt009

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multimerization of anti-(epidermal growth factor receptor) IgG fragments induces an antitumor effect: the case for humanized 528 scFv multimers2013

    • Author(s)
      Ryutaro Asano, el al.
    • Journal Title

      FEBS J.

      Volume: 280 Issue: 19 Pages: 4816-4826

    • DOI

      10.1111/febs.12451

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 抗体医薬品開発の最前線: トレンドと課題2016

    • Author(s)
      浅野竜太郎
    • Organizer
      福島県病院薬剤師会 1月福島支部学術講演会
    • Place of Presentation
      ホテルサンルートプラザ福島(福島県福島市)
    • Year and Date
      2016-01-20
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 抗体医薬品開発の課題とトレンド2015

    • Author(s)
      浅野竜太郎
    • Organizer
      Biologics Expert Meeting in Hokkaido
    • Place of Presentation
      ニューオータニイン札幌(北海道札幌市)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 抗体医薬品開発の現状と展望 ~タンパク質工学の寄与~2015

    • Author(s)
      浅野竜太郎
    • Organizer
      第176回 熊本県病院薬剤師会研修会
    • Place of Presentation
      熊本大学医学部付属病院(熊本市中央区)
    • Year and Date
      2015-09-05
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 抗体医薬品開発の現状と次世代人工抗体の可能性2015

    • Author(s)
      浅野竜太郎
    • Organizer
      Biologics Seminar for Pharmacist in Sendai
    • Place of Presentation
      江陽グランドホテル (仙台)
    • Year and Date
      2015-03-17
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Fc融合二重特異性抗体のドメイン組換えによるin vivo抗腫瘍効果の増強2015

    • Author(s)
      浅野竜太郎
    • Organizer
      平成26年度「個体レベルでのがん研究支援活動」ワークショップ
    • Place of Presentation
      琵琶湖ホテル (大津)
    • Year and Date
      2015-02-06
    • Related Report
      2014 Research-status Report
  • [Presentation] がん細胞成長阻害活性を有する多量体化抗EGFR一本鎖抗体の精密機能解析2014

    • Author(s)
      浅野竜太郎
    • Organizer
      第66回日本生物工学会大会
    • Place of Presentation
      札幌コンベンションセンター (札幌)
    • Year and Date
      2014-09-11
    • Related Report
      2014 Research-status Report
  • [Presentation] がん治療スマート抗体の迅速設計を目指したスクリーニング法の開発2014

    • Author(s)
      杉山在生人
    • Organizer
      平成26年度 がん若手研究者ワークショップ
    • Place of Presentation
      蓼科グランドホテル (蓼科)
    • Year and Date
      2014-09-05 – 2014-09-12
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒト上皮増殖因子受容体を標的とした多価抗体の開発2014

    • Author(s)
      浅野竜太郎
    • Organizer
      化学療法基盤支援活動第3回シンポジウム
    • Place of Presentation
      万国津梁館 (名護)
    • Year and Date
      2014-05-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 低分子二重特異性がん治療抗体のドメイン組換えによるin vivo抗腫瘍効果の増強2014

    • Author(s)
      浅野竜太郎
    • Organizer
      平成25年度「個体レベルでのがん研究支援活動」ワークショップ
    • Place of Presentation
      琵琶湖ホテル (大津)
    • Related Report
      2013 Research-status Report
  • [Presentation] 二重特異性抗体のタンパク質工学を駆使した高機能化2014

    • Author(s)
      浅野竜太郎
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学 文学部 (熊本)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Cytotoxic enhancement of a small bispecific antibody with specificity for EGFR and CD3 by rearranging a domain order2013

    • Author(s)
      Ryutaro Asano
    • Organizer
      ICSG2013-SLS
    • Place of Presentation
      京王プラザホテル札幌 (札幌)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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