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Search for traditional drugs and naturally derived compounds that act on immune checkpoints and analyze their effectiveness

Research Project

Project/Area Number 19K16393
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47050:Environmental and natural pharmaceutical resources-related
Research InstitutionShimane University

Principal Investigator

Kotani Hitoshi  島根大学, 学術研究院医学・看護学系, 講師 (10594640)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords免疫チェックポイント / 生薬 / 天然物 / PD-1 / PD-L1 / 低分子化合物 / タンパク質間相互作用 / T細胞 / 免疫疲弊 / スクリーニング / 老化 / 癌 / 伝統医薬品
Outline of Research at the Start

本研究は、免疫チェックポイントに作用する天然由来化合物・伝統医薬品の探索とその有効性の解析をおこなうことを目的とする。実験計画としては、① PD-1/PD-L1相互作用の阻害活性評価系作製 ② 伝統医薬品・植物エキスのスクリーニング ③ 活性成分の探索 ④ in vitroの解析(免疫細胞活性化の評価)⑤ in vivo有効性評価(抗腫瘍活性の動物実験)をおこない、より経済負担が少なく安定性の高い免疫チェックポイント阻害剤を開発し、多くの国民が安価に新しい免疫チェックポイント治療を受けることが可能となることを大きな目標とする。

Outline of Final Research Achievements

In this research, we focused on the mechanism newly discovered in the development of cutting-edge medical technology, and searched for traditional medicines and naturally derived compounds with similar mechanism. However, as a result of research, it has become clear that it is difficult to find a drug that acts as specifically as an antibody drug, and it is difficult to easily replace the antibody drug. However, the decline in immunity with aging and the prevention and treatment of age-related diseases are important issues that should be addressed in a super-aging society, and it is also necessary to develop drugs by an indirect method different from antibody drugs.

Academic Significance and Societal Importance of the Research Achievements

本研究により、抗体医薬品などが特異性が高く、容易に同等なメカニズムを持つ低分子化合物の発見をすることは難しいことが明らかとなった。その点において、高価な抗体医薬品などの生物学的製剤の有用性が示された。しかし、低分子製剤や伝統医薬品など安定性が高く、安価であり、経口投与が可能な医薬品のほうが多くの人々にとって有用であることは間違いないことから、このような医薬品の新しいメカニズムの解析研究も見直されるべきである。最先端の医薬品と昔ながらな医薬品の両輪を進めながら医薬品開発を進める必要がある。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (14 results)

All 2022 2021 2020 2019

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (7 results)

  • [Journal Article] Protective role of cytoplasmic p21Cip1/Waf1 in apoptosis of CDK4/6 inhibitor‐induced senescence in breast cancer cells2021

    • Author(s)
      Kartika Irna D.、Kotani Hitoshi、Iida Yuichi、Koyanagi Akira、Tanino Ryosuke、Harada Mamoru
    • Journal Title

      Cancer Medicine

      Volume: 10 Issue: 24 Pages: 8988-8999

    • DOI

      10.1002/cam4.4410

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] T-cell responses and combined immunotherapy against human carbonic anhydrase 9-expressing mouse renal cell carcinoma2021

    • Author(s)
      Harada Mamoru、Iida Yuichi、Kotani Hitoshi、Minami Takafumi、Komohara Yoshihiro、Eto Masatoshi、Yoshikawa Kazuhiro、Uemura Hirotsugu
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: 71 Issue: 2 Pages: 339-352

    • DOI

      10.1007/s00262-021-02992-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunogenic chemotherapy in two mouse colon cancer models2020

    • Author(s)
      Taniura Takahito、Iida Yuichi、Kotani Hitoshi、Ishitobi Kazunari、Tajima Yoshitsugu、Harada Mamoru
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 10 Pages: 3527-3539

    • DOI

      10.1111/cas.14624

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Local injection of CCL19-expressing mesenchymal stem cells augments the therapeutic efficacy of anti-PD-L1 antibody by promoting infiltration of immune cells2020

    • Author(s)
      Iida Yuichi、Yoshikawa Rintaro、Murata Akihiko、Kotani Hitoshi、Kazuki Yasuhiro、Oshimura Mitsuo、Matsuzaki Yumi、Harada Mamoru
    • Journal Title

      Journal for ImmunoTherapy of Cancer

      Volume: 8 Issue: 2 Pages: e000582-e000582

    • DOI

      10.1136/jitc-2020-000582

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Supplementation of l ‐arginine boosts the therapeutic efficacy of anticancer chemoimmunotherapy2020

    • Author(s)
      Satoh Yusuke、Kotani Hitoshi、Iida Yuichi、Taniura Takahito、Notsu Yoshitomo、Harada Mamoru
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 7 Pages: 2248-2258

    • DOI

      10.1111/cas.14490

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pemetrexed Sensitizes Human Lung Cancer Cells to Cytotoxic Immune Cells2020

    • Author(s)
      Okimoto T, Kotani H, Iida Y, Koyanagi A, Tanino R, Tsubata Y, Isobe T, Harada M.
    • Journal Title

      Cancer Sci.

      Volume: ー Issue: 6 Pages: 1910-1920

    • DOI

      10.1111/cas.14401

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Different Sensitivities of Senescent Breast Cancer Cells to Immune Cell-Mediated Cytotoxicity2019

    • Author(s)
      Inao T, Kotani H, Iida Y, Kartika ID, Okimoto T, Tanino R, Shiba E, Harada M.
    • Journal Title

      Cancer Sci.

      Volume: 110(9) Issue: 9 Pages: 2690-2699

    • DOI

      10.1111/cas.14116

    • NAID

      120007002176

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ミャンマー産植物からのBMP/Smadシグナル活性成分の探索2022

    • Author(s)
      矢作忠弘、渡辺美咲、今依麻、小谷仁司、松野倫代、川原信夫、松崎桂一
    • Organizer
      日本薬学会第142年会(名古屋)
    • Related Report
      2021 Annual Research Report
  • [Presentation] エストロゲン受容体活性化作用を有する琉球弧植物の骨代謝への影響2022

    • Author(s)
      渡辺美咲、福富遥都、矢作忠弘、三宅克典、小谷仁司、小川拓哉、松崎桂一
    • Organizer
      日本薬学会第142年会(名古屋)
    • Related Report
      2021 Annual Research Report
  • [Presentation] アカボシタツナミソウのBMP/Smadシグナル活性化成分の探索2022

    • Author(s)
      渡辺美咲、福富遥都、矢作忠弘、上倉りな、三宅克典、小谷仁司、松崎桂一
    • Organizer
      日本薬学会第142年会(名古屋)
    • Related Report
      2021 Annual Research Report
  • [Presentation] 老化誘導剤アフィジコリンと老化細胞除去薬ABT-263のヒト乳がんと肺がん細胞に対する併用効果2021

    • Author(s)
      小谷仁司、谷野良輔、飯田雄一、原田守
    • Organizer
      第80回日本癌学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] エストロゲン受容体を標的とした骨形成促進作用を示す琉球弧植物の探索2021

    • Author(s)
      渡辺美咲、矢作忠弘、白山貴大、三宅克典、小谷仁司、松﨑桂一
    • Organizer
      日本生薬学会第67回年会(東京)
    • Related Report
      2021 Annual Research Report
  • [Presentation] 老化誘導剤アフィジコリンと老化細胞除去薬ABT-263による乳癌細胞に対する新しい組み合わせ治療2020

    • Author(s)
      小谷仁司、飯田雄一、原田守
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Identification of a candidate that suppresses the differentiation of naive helper T cells to regulatory T cells via screening of herbal crude drugs2019

    • Author(s)
      Hitoshi Kotani, Yuichi Iida, Mamoru Harada
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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