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Development of an anticancer therapy against liver cancer using 2-deoxy-D-glucose encapsulated in polymer poly (lactic-co-glycolic acid) nanoparticles

Research Project

Project/Area Number 18K07923
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKawasaki Medical School

Principal Investigator

Nishina Sohji  川崎医科大学, 医学部, 准教授 (70550961)

Co-Investigator(Kenkyū-buntansha) 原 裕一  川崎医科大学, 医学部, 講師 (60550952)
日野 啓輔  川崎医科大学, 医学部, 教授 (80228741)
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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsがん / 解糖系 / ドラッグデリバリー / ナノ粒子 / 腫瘍免疫 / 肝細胞癌 / 解糖系阻害剤 / 2-Deoxy-D-Glucose(2DG) / 2DG-PLGA-NP / 抗腫瘍免疫 / 2DG / PLGA / 2-Deoxy-D-Glucose / drug delivery system
Outline of Final Research Achievements

The 2DG-PLGA-NPs induced cytotoxic effects and antitumor immunity through enhanced T cell trafficking. Additionally, 2DG-PLGA-NPs induced decreased lactate production and increased IFNγ-positive T cells in liver tumors. Human CD8+ T cells cocultured with 2DG-PLGA-NP-treated Huh7 cells revealed their increased IFNγ production and glucose uptake compared to the CD8+ T cells cocultured with PLGA-NP-treated Huh7 cells. Chemotaxis of CD8+ T cells was suppressed by lactate and enhanced by glucose. IFNγ enhanced CD8+ T cell chemotaxis in both an autocrine and paracrine manner. Notably, the 2DG-PLGA-NPs augmented chemokine (CXCL9-11) production in liver tumors via IFNγ/STAT pathway and AMPK-mediated suppression of histone H3 lysine 27 trimethylation. These 2DG-PLGA-NPs not only amplified antitumor effects induced by anti-PD1 antibody but also suppressed anti-PD1-resistant tumors.

Academic Significance and Societal Importance of the Research Achievements

がん研究において腫瘍免疫は最もactiveかつcompetitiveな分野のひとつである。また、がん代謝とがん微小環境における腫瘍免疫との関連についての研究も盛んに行われている。2DG-PLGA-NPによるがん特異的な糖代謝阻害作用は、現在実用化されている抗PD-1抗体等の免疫チェックポイント阻害剤とは異なる作用機序で腫瘍免疫を活性化する可能性があり、また肝細胞癌以外のがん治療に応用できる可能性がある。

Report

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

    (12 results)

All 2021 2020 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 5 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Nanoparticle-Mediated Delivery of 2-Deoxy-D-Glucose Induces Antitumor Immunity and Cytotoxicity in Liver Tumors in Mice2021

    • Author(s)
      Sasaki Kyo、Nishina Sohji、Yamauchi Akira、Fukuda Kotaro、Hara Yuichi、Yamamura Masahiro、Egashira Kensuke、Hino Keisuke
    • Journal Title

      Cellular and Molecular Gastroenterology and Hepatology

      Volume: 11 Issue: 3 Pages: 739-762

    • DOI

      10.1016/j.jcmgh.2020.10.010

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] がん特異的解糖系阻害剤による肝細胞癌治療応用と腫瘍免疫活性化機構の解明2020

    • Author(s)
      仁科惣治、佐々木恭、日野啓輔
    • Organizer
      第56回 日本肝臓学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肝細胞癌の糖代謝抑制による腫瘍免疫賦活化と治療展開2020

    • Author(s)
      仁科惣治、佐々木恭、日野啓輔
    • Organizer
      第106回 日本消化器病学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 2-deoxy-D-glucose encapsulated PLGA nanoparticles suppress hepatocellular carcinoma through cytotoxic effect and activation of antitumor immunity2020

    • Author(s)
      Sohji Nishina, Kyo Sasaki, Akira Yamauchi, Kotaro Fukuda, Keisuke Hino
    • Organizer
      American Association for the Study of Liver Diseases (AASLD)-The Liver Meeting 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Specific inhibition of cancer cell glycolysis enhances antitumor immunity in hepatocellular carcinoma2019

    • Author(s)
      佐々木恭、仁科惣治、山内明、原裕一、福田宏太郎、日野啓輔
    • Organizer
      APASL Single Topic Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Treatment of hepatocellular carcinoma using 2-Antitumor effects of 2-deoxy-D-glucose encapsulated PLGA nanoparticles against hepatocellular carcinoma in terms of tumor immunity2019

    • Author(s)
      佐々木恭、仁科惣治、山内明、原裕一、福田宏太郎、日野啓輔
    • Organizer
      American Association for the Study of Liver Diseases(AASLD) Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Immuno oncologyからみた肝細胞癌に対する2-deoxyD-glucose封入PLGAナノ粒子の抗腫傷効果2019

    • Author(s)
      佐々木恭、仁科惣治、日野啓輔
    • Organizer
      日本消化器病学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 肝癌細胞の糖代謝抑制によるがん微小環境での腫瘍免疫賦活作用とその臨床応用2019

    • Author(s)
      佐々木恭、仁科惣治、日野啓輔
    • Organizer
      日本肝臓学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 肝糖代謝阻害薬2-deoxy-D-glucose封入PLGAナノ粒子を用いた肝細胞癌治療開発2018

    • Author(s)
      佐々木恭、仁科惣治、日野啓輔ら
    • Organizer
      Japan Digestive Disease Week 2018 (JDDW 2018)
    • Related Report
      2018 Research-status Report
  • [Presentation] Treatment of hepatocellular carcinoma using 2-deoxy-D-glucose encapsulated in PLGA nanoparticles in mice2018

    • Author(s)
      佐々木恭、仁科惣治、日野啓輔ら
    • Organizer
      APASL Single Topic Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Treatment of hepatocellular carcinoma using 2-deoxy-D-glucose encapsulated in PLGA nanoparticles in mice2018

    • Author(s)
      佐々木恭、仁科惣治、日野啓輔ら
    • Organizer
      American Association for the Study of Liver Diseases(AASLD) Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] ケモカイン産生促進剤、免疫チェックポイント阻害剤抵抗性癌治療薬及び抗腫瘍免疫賦活剤」2019

    • Inventor(s)
      日野啓輔、仁科惣治、佐々木恭、山内明
    • Industrial Property Rights Holder
      日野啓輔、仁科惣治、佐々木恭、山内明
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-048743
    • Filing Date
      2019
    • Related Report
      2018 Research-status Report

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

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