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Development of combined immunochemotherapy to restructure the tumour immune microenvironment in advanced pancreatic cancer

Research Project

Project/Area Number 22K08088
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionJikei University School of Medicine

Principal Investigator

Koido Shigeo  東京慈恵会医科大学, 医学部, 非常勤講師 (70266617)

Co-Investigator(Kenkyū-buntansha) 村橋 睦了 (伊賀睦了)  東京慈恵会医科大学, 医学部, 教授 (20422420)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsWT1 / 膵癌 / 免疫化学療法 / ワクチン / conversion surgery / 樹状細胞 / 樹状細胞ワクチン / 腫瘍免疫微小環境 / neoantigen / 膵臓癌
Outline of Research at the Start

現在実施している以下の臨床試験に関して、詳細な免疫モニタリングを網羅的に実施し、膵癌患者の腫瘍免疫微少環境(TME)と治療効果の関連性を評価する。最終的に、TMEにおける免疫担当細胞の再構築による新規複合的免疫化学療法の開発を目指す。
①「切除不能膵癌に対する標準化学療法併用Neoantigen樹状細胞ワクチン療法」(jRCTc030190081)
②「切除不能膵癌に対する標準化学療法併用WT1樹状細胞ワクチン療法」(jRCTc030190195)

Outline of Final Research Achievements

We are conducting two clinical trials: 'WT1 Dendritic Cell Vaccine Therapy with Standard Chemotherapy for Unresectable Pancreatic Cancer' (JRCSTSTE001000001) and 'Neoantigen Dendritic Cell Vaccine Therapy with Standard Chemotherapy for Unresectable Pancreatic Cancer' (JRCSTSTE001000002). The former trial involved detailed immune monitoring to evaluate the relationship between the tumour immune microenvironment (TME) and therapeutic efficacy in patients with pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

(1)臨床転帰の評価が可能だった9名における全生存期間中央値は3.52年、無増悪生存期間中央値は2.23年だった。(2)切除不能進行膵癌10名中7名が手術可能となった。著しく治療効果が認められた4名は、WT1に対する強い免疫反応が長期間誘導・維持できていた。(3)手術が可能となった腫瘍局所には抗腫瘍免疫に関連するリンパ球が多く集簇していた。一方、抑制性T細胞の集簇は少なかった。以上から、これまで有効な治療法が無かった切除不能膵癌に対して、WT1樹状細胞ワクチンと標準化学療法(ゲムシタビン・ナブパクリタキセル)を併用した新規免疫化学療法は有望な治療法となる可能性が期待された。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (3 results)

All 2024 2022

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results)

  • [Journal Article] Dendritic cells pulsed with multifunctional Wilms’ tumor 1 (WT1) peptides combined with multiagent chemotherapy modulate the tumor microenvironment and enable conversion surgery in pancreatic cancer2024

    • Author(s)
      Koido Shigeo、Taguchi Junichi、Shimabuku Masamori、Kan Shin、Bito Tuuse、Misawa Takeyuki、Ito Zensho、Uchiyama Kan、Saruta Masayuki、Tsukinaga Shintaro、Suka Machi、Yanagisawa Hiroyuki、Sato Nobuhiro、Ohkusa Toshifumi、Shimodaira Shigetaka、Sugiyama Haruo
    • Journal Title

      Journal for ImmunoTherapy of Cancer

      Volume: 12 Issue: 10 Pages: e009765-e009765

    • DOI

      10.1136/jitc-2024-009765

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The stimulatory effect of fusobacteria on dendritic cells under aerobic or anaerobic conditions2022

    • Author(s)
      Koido Shigeo、Horiuchi Sankichi、Kan Shin、Bito Tsuuse、Ito Zensho、Uchiyama Kan、Saruta Masayuki、Sato Nobuhiro、Ohkusa Toshifumi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 10698-10698

    • DOI

      10.1038/s41598-022-14934-z

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Detection of Immunity against WT1 and SMAD4P130L of EpCAM+ Cancer Cells in Malignant Pleural Effusion2022

    • Author(s)
      Koya Terutsugu、Niida Yo、Togi Misa、Yoshida Kenichi、Sakamoto Takuya、Ura Hiroki、Togi Sumihito、Kato Tomohisa、Yamada Sohsuke、Sugiyama Haruo、Koido Shigeo、Shimodaira Shigetaka
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 20 Pages: 12177-12177

    • DOI

      10.3390/ijms232012177

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2022-04-19   Modified: 2026-01-16  

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