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Combination therapy of anti-PD-1 monoclonal antibody with REIC gene therapy for pancreatic cancer

Research Project

Project/Area Number 19K17462
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionOkayama University

Principal Investigator

Uchida Daisuke  岡山大学, 大学病院, 講師 (50749215)

Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywords遺伝子治療 / REIC遺伝子 / 難治性消化器癌 / 腫瘍免疫 / ICI / REIC / PD-1 / DKK3 / DKK-3 / REIC/Dkk-3 / 膵癌 / 胆管癌
Outline of Research at the Start

REIC遺伝子治療は、様々な癌腫に対する抗腫瘍効果が報告されている。近年注目されている免疫チェックポイント阻害薬に関しては、REIC遺伝子治療の抗腫瘍効果の一つである腫瘍免疫の誘導を増強することが期待される。本研究では、胆道癌、膵癌などの難治癌における免疫チェックポイント阻害薬を併用したREIC遺伝子導入治療による抗腫瘍効果の検証を行い、臨床応用可能な治療法の開発を目指す。

Outline of Final Research Achievements

We investigated the combined effect of Ad-SGE-REIC and ICI in pancreatic cancer cell lines, biliary tract cancer cell lines, and colorectal cancer cell lines. In vitro, while the efficacy of anti-PD-1 antibody was not fully validated, a certain trend of enhanced efficacy was observed. In vivo validation involved creating a transplant model of Colon-26, a syngeneic colorectal cancer cell line, and assessing tumor immune induction including the abscopal effect with combined Ad-SGE-REIC and ICI. While a local effect of Ad-SGE-REIC was observed, the strong tumor suppressive effect of PD-1 antibody monotherapy overshadowed the potential synergistic effect of combination therapy, thus failing to demonstrate sufficient synergistic effects.

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害薬や分子標的薬をはじめとした様々ながん化学療法が進歩しているが、難治性消化器癌の根治性はまだ十分とはいえない。本研究において検証した遺伝子治療は、がん治療の新たな治療選択肢の一つとして注目されており、岡山大学において発見されたREIC/Dkk-3は治療ターゲットとして有望ながん関連遺伝子として研究開発が進められてきた。本研究では胆膵がんを中心とした難治性消化器癌における遺伝子治療の可能性を示す有用なデータが蓄積された。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2020 2019

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

  • [Journal Article] Promising gene therapy using an adenovirus vector carrying REIC/Dkk-3 gene for the treatment of biliary cancer.2020

    • Author(s)
      Emi Tanaka,Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Atsushi Oyama, Masaya Iwamuro, Masami Watanabe, Hiromi Kumon, Hiroyuki Okada
    • Journal Title

      Current Gene Therapy

      Volume: - Issue: 1 Pages: 64-70

    • DOI

      10.2174/1566523220666200309125709

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The Efficacy of REIC/Dkk-3 Gene Therapy for Pancreaticobiliary Carcinoma2019

    • Author(s)
      Daisuke Uchida, Hidenori Shiraha, Emi Tanaka, Hironari Kato, Hiroyuki Okada
    • Organizer
      UEG week 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2025-01-30  

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