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Antibody-dependent cellular cytotoxicity with defucosylated monoclonal antibodies in patients with GI-tract cancer

Research Project

Project/Area Number 17K10597
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionFukushima Medical University

Principal Investigator

Nakajima Takahiro  福島県立医科大学, 医学部, 博士研究員 (90567447)

Co-Investigator(Kenkyū-buntansha) 河野 浩二  福島県立医科大学, 医学部, 教授 (40283204)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsADCC / 抗体治療 / 免疫治療 / 胃癌 / 脱フコシル化 / 抗体 / 脱フコシル化抗体 / 抗体依存性細胞障害 / 医学 / 癌
Outline of Final Research Achievements

Although herceptin and rituximab are a standard treatment for breast and gastric cancer and lymphoma, their efficacy is still limited. In this study, trastuzumab- and cetuximab-mediated ADCC by comparing defucosylated mAbs with conventional mAbs using peripheral blood mononuclear cells (PBMCs) were performed. When the defucosylated mAbs were used instead of the conventional mAbs, the ADCC activities in the advanced cancer cases were almost comparable with those in early disease or healthy individuals.In conclusion, defucosylated therapeutic mAbs can enhance ADCC activities in patients with cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究では、消化管癌において、既存の抗体医薬に比し脱フコシル化抗体の有効性を示すことを目標とし、消化器癌患者20名から末梢血リンパ球を分離し、脱フコシル化ハーセプチンと、脱フコシル化セツキシマブを用いたADCCを検討し、脱フコシル化抗体が、有意にADCCを増強させることを突き止めた。この成果は、消化器癌領域において、抗体医薬の治療効果増強に大きく寄与し、癌治療の向上に役立つ。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (1 results)

  • [Journal Article] A subset of patients with MSS/MSI?low?colorectal cancer showed increased CD8(+) TILs together with up?regulated IFN?γ2019

    • Author(s)
      Kikuchi Tomohiro、Mimura Kosaku、Okayama Hirokazu、Nakayama Yuko、Saito Katsuharu、Yamada Leo、Endo Eisei、Sakamoto Wataru、Fujita Shotaro、Endo Hisahito、Saito Motonobu、Momma Tomoyuki、Saze Zenichiro、Ohki Shinji、Kono Koji
    • Journal Title

      Oncology Letters

      Volume: 66 Pages: 10-66

    • DOI

      10.3892/ol.2019.10953

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of tumor-infiltrating immune cells in relation to microbiota in colorectal cancers2019

    • Author(s)
      Kikuchi Tomohiro、Mimura Kosaku、Ashizawa Mai、Okayama Hirokazu、Endo Eisei、Saito Katsuharu、Sakamoto Wataru、Fujita Shotaro、Endo Hisahito、Saito Motonobu、Momma Tomoyuki、Saze Zenichiro、Ohki Shinji、Shimada Kazunori、Yoshimura Kiyoshi、Tsunoda Takuya、Kono Koji
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: 69 Issue: 1 Pages: 23-32

    • DOI

      10.1007/s00262-019-02433-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] KRT17 as a prognostic biomarker for stage II colorectal cancer2019

    • Author(s)
      Ujiie Daisuke、Okayama Hirokazu、Saito Katsuharu、Ashizawa Mai、Thar Min Aung Kyi、Endo Eisei、Kase Koji、Yamada Leo、Kikuchi Tomohiro、Hanayama Hiroyuki、Fujita Shotaro、Sakamoto Wataru、Endo Hisahito、Saito Motonobu、Mimura Kosaku、Saze Zenichiro、Momma Tomoyuki、Ohki Shinji、Kono Koji
    • Journal Title

      Carcinogenesis

      Volume: 0 Issue: 5 Pages: 0-0

    • DOI

      10.1093/carcin/bgz192

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Augmentation of Antibody-Dependent Cellular Cytotoxicity with defucosylated monoclonal antibodies in patients with GI-tract cancer2018

    • Author(s)
      26.Takahiro Nakajima, Hirokazu Okayama, Mai Ashizawa, Masaru Noda, Keita Aoto, Motonobu Saito, Tomoyuki Monma, Shinji Ohki, Masahiko Shibata, Seiichi Takenoshita and Koji Kono
    • Journal Title

      Oncology Letters

      Volume: 15 Pages: 2604-2610

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Augmentation of antibody-dependent cellular cytotoxicity with defucosylated monoclonal antibodies in patients with GI-tract cancer2018

    • Author(s)
      Nakajima Takahiro、Okayama Hirokazu、Ashizawa Mai、Noda Masaru、Aoto Keita、Saito Motonobu、Monma Tomoyuki、Ohki Shinji、Shibata Masahiko、Takenoshita Seiichi、Kono Koji
    • Journal Title

      Oncology Letters

      Volume: 15 Pages: 2604-2610

    • DOI

      10.3892/ol.2017.7556

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunogenic tumor cell death induced by chemotherapy in patients with breast cancer and esophageal squamous cell carcinoma2018

    • Author(s)
      Aoto Keita、Mimura Kousaku、Okayama Hirokazu、Saito Motonobu、Chida Shun、Noda Masaru、Nakajima Takahiro、Saito Katsuharu、Abe Noriko、Ohki Shinji、Ohtake Tohru、Takenoshita Seiichi、Kono Koji
    • Journal Title

      Oncology Reports

      Volume: 39 Pages: 151-159

    • DOI

      10.3892/or.2017.6097

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 脱フコシル化抗体を用いたADCCの検討2017

    • Author(s)
      中島 隆宏,河野 浩二,芦澤 舞,千田 峻,野田 勝,青砥 慶太,立花 和之進,岡山 洋和,早瀬 傑,坂本 渉,石亀 輝英,齋藤 元伸,志村 龍男,大竹 徹,竹之下 誠一
    • Organizer
      第117回日本外科学会定期学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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