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Development of Next-Generation Immunotherapy using Antitumor Antibodies armed with Bridging-BiTE against Refractory Tumors

Research Project

Project/Area Number 18K08331
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionEhime University

Principal Investigator

Ochi Toshiki  愛媛大学, 医学系研究科, 講師 (10571086)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsがん免疫療法 / 二重特異性抗体 / 改変抗体 / 造血器腫瘍
Outline of Final Research Achievements

In this study, we have developed a new modality, named as B-BiTE (Bridging-Bispecific T-cell Engager) by using gene-engineering technology. B-BiTE possesses two single chain fragment variables (scFvs) which are specific for human IgG-Fc and human CD3, respectively. B-BiTE can bind to an antitumor antibody, thereby generating a new bispecific antibody. A mAb/B-BiTE complex can activate human T cells while preserving human NK-cell reactivity which is mediated by a mAb itself. Therefore, a mAb/B-BiTE complex can induce enhanced in vivo antitumor effects as compared to those mediated by a mAb alone. B-BiTE can allow us to develop a panel of new bispecific antibodies from a series of clinically available mAbs, resulting in further advancement of next-generation antibody-based cancer immunotherapy.

Academic Significance and Societal Importance of the Research Achievements

免疫療法は、難治性がんに対する新たな治療法として注目されているが、高額な費用が必要となることなど、多くのがん患者に還元するにはまだ多くの問題を抱えている。我々が確立した新規技術 -B-BiTE- を用いれば、これまでに開発された、またこれから開発される抗体医薬品にあらかじめB-BiTEを結合させるだけで、新たな二重特異性抗体を迅速かつ容易に作製することが可能となる。本技術によって、コストを抑えつつ、がん免疫療法の治療効果を幅広く増強することが期待できるため、免疫療法医薬品開発領域におけるインパクトは大きく、社会的意義も高いと考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (21 results)

All 2021 2019 2018 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (3 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Direct comparisoin of target-reactivity and cross-reactivity induced by CAR-and BiTE-redirected T cells for the development of antibody-based T-cell therapy.2019

    • Author(s)
      Masaki Maruta, Toshiki Ochi, Kazushi Tanimoto, Hiroaki Asai, et al.
    • Journal Title

      Scientific reports

      Volume: 9 Issue: 1 Pages: 13293-13293

    • DOI

      10.1038/s41598-019-49834-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of innovative T-cell immunotherapy for hematological malignancies2019

    • Author(s)
      Ochi T
    • Journal Title

      Rinsho Ketsueki

      Volume: 60 Issue: 7 Pages: 824-833

    • DOI

      10.11406/rinketsu.60.824

    • NAID

      130007687999

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] DEVELOPMENT OF NEXT-GENERATION ANTITUMOR ANTIBODIES ARMED WITH BRIDGING-BITE TO ADVANCE ANTI-MYELOMA IMMUNOTHERAPY2021

    • Author(s)
      Konishi T, Ochi T, Maruta M, Tanimoto K, Saitou T, Imamura T, Yasukawa M, Takenaka K.
    • Organizer
      European Hematology Association
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of innovative antitumor antibodies armed with Bridging-BiTE to advance anti-myeloma immunotherapy2021

    • Author(s)
      Konishi T, Ochi T, Maruta M, Tanimoto K, Saitou T, Imamura T, Yasukawa M, Takenaka K.
    • Organizer
      第46回日本骨髄腫学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Development of novel bispecific antibodies armed with Bridging-BiTE for targeting a variety of tumors2021

    • Author(s)
      Konishi T, Ochi T, Maruta M, Tanimoto K, Saitou T, Imamura T, Yasukawa M, Takenaka K.
    • Organizer
      第25回日本がん免疫学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 難治性骨髄腫に対する新規治療を目指した次世代型遺伝子改変二重特異性抗体の開発2021

    • Author(s)
      小西 達矢, 越智 俊元, 丸田 雅樹, 谷本 一史, 齋藤 卓, 今村 健志, 安川 正貴, 竹中 克斗
    • Organizer
      第13回日本血液疾患免疫療法学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Establishment of a novel T-cell-based scFv screening technology to advance modified antibody-based immunotherapy.2019

    • Author(s)
      Ochi T, Maruta M, Tanimoto K, Fujiwara H, Takenaka K, Yasukawa M
    • Organizer
      The 17th Annual Meeting of the Association for Cancer Immunotherapy (CIMT)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 免疫療法の未来を拓く次世代型抗体の開発とその応用2019

    • Author(s)
      越智俊元
    • Organizer
      日本骨髄腫学会 第1回骨髄腫セミナー
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Next-generation CAR T-cell therapy using antitumor scFvs optimized by a cell-based screening system.2019

    • Author(s)
      Ochi T, Maruta M, Tanimoto K, Fujiwara H, Takenaka K, Yasukawa M
    • Organizer
      The 81st Annual Meeting of the Japanese Society of Hematology
    • Related Report
      2019 Research-status Report
  • [Presentation] キメラ抗原受容体導入細胞傷害性T細胞におけるCD8分子の役割2019

    • Author(s)
      近藤史孟, 越智俊元, 丸田雅樹, 谷本一史, 竹中克斗, 安川正貴
    • Organizer
      第116回日本内科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] A novel scFv screening technology by exploiting T cells in combination with CAR-based scFv library.2019

    • Author(s)
      越智俊元, 丸田雅樹, 谷本一史, 藤原弘, 竹中克斗, 安川正貴
    • Organizer
      第23回日本がん免疫学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Development of next-generation CAR-T cell therapy using antitumor scFvs optimized by a novel cell-based screening system.2019

    • Author(s)
      越智俊元, 丸田雅樹, 谷本一史, 藤原弘, 竹中克斗, 安川正貴
    • Organizer
      第11回日本血液疾患免疫療法学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Generation of optimal antitumor receptors for T-cell therapy in hematological malignancies. Symposium 7, -Rising star in JSH-2018

    • Author(s)
      Toshiki Ochi
    • Organizer
      The 80th Annual Meeting of the Japanese Society of Hematology
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 臨床ニーズに即したがん免疫療法を目指す新規改変抗体の開発研究2018

    • Author(s)
      越智俊元, 丸田雅樹, 谷本一史, 朝井洋晶, 斉藤卓, 今村健志, 竹中克斗, 安川正貴
    • Organizer
      第6回TR推進合同フォーラム・ライフサイエンス技術交流会
    • Related Report
      2018 Research-status Report
  • [Presentation] 改変抗体を応用したがんに対する新規免疫療法の開発研究2018

    • Author(s)
      越智俊元
    • Organizer
      第2回先進医薬研究報告会
    • Related Report
      2018 Research-status Report
  • [Book] Methods in Molecular Biology.2019

    • Author(s)
      Ochi T, Maruta M, Hirano N.
    • Total Pages
      267
    • Publisher
      Springer
    • ISBN
      9781493997275
    • Related Report
      2019 Research-status Report
  • [Book] 実験医学2019

    • Author(s)
      越智俊元, 安川正貴
    • Total Pages
      267
    • Publisher
      羊土社
    • ISBN
      9784758103817
    • Related Report
      2019 Research-status Report
  • [Book] 血液疾患 最新の治療2020-20222019

    • Author(s)
      越智俊元
    • Total Pages
      384
    • Publisher
      南江堂
    • ISBN
      9784524249787
    • Related Report
      2019 Research-status Report
  • [Remarks] 最先端研究紹介 infinity 免疫の力で白血病を治そう!

    • URL

      https://www.ehime-u.ac.jp/data_study/data_study-100509/

    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 複合体化タンパク質、抗体複合体、医薬組成物、および核酸2019

    • Inventor(s)
      越智俊元、安川正貴、竹中克斗
    • Industrial Property Rights Holder
      越智俊元、安川正貴、竹中克斗
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 複合体化タンパク質、抗体複合体、医薬組成物、および核酸2019

    • Inventor(s)
      越智俊元、安川正貴、竹中克斗
    • Industrial Property Rights Holder
      越智俊元、安川正貴、竹中克斗
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-024976
    • Filing Date
      2019
    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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