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Development of the killing function of iPSC derived CAR-T cell for solid tumor.

Research Project

Project/Area Number 20K16439
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Mishima Yuta  筑波大学, 医学医療系, 助教 (80770263)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsがん免疫治療 / IPS細胞 / CAT-T細胞治療 / マイクロ流体デバイス / 免疫細胞分化 / AI画像解析 / CAR-T細胞 / がん免疫細胞療法 / 遺伝子治療 / 再生T細胞 / iPS細胞 / Tumor-on-a-chip / がん免疫 / Immunotherapy / 再生医療 / iPS cell / CAR-T therapy / Microdevice / Cancer Immunotherapy / immunotherapy
Outline of Research at the Start

固形がんにおけるがん免疫において、体の局所に存在する腫瘍を特異的に傷害するためには、血液がんのそれとは異なり、免疫細胞が血管を通って遊走し、腫瘍組織への浸潤の後、標的を認識し、活性化と増殖を通して傷害するプロセスが必要である。従って、免疫T細胞の腫瘍への遊走能力や浸潤能力がいかにして制御されているか、そのメカニズムと細胞傷害性効果との関係を明らかにすることができれば、固形がんにおけるがん免疫療法の抗腫瘍効果を向上させることが可能と考えられる。本研究では独自に開発した3つの新規技術をツールとして用いることにより、固形がんにおけるT細胞の遊走能力や浸潤能力の制御メカニズムの解明に取り組む。

Outline of Final Research Achievements

This investigation sought to identify crucial genes that enhance three fundamental capabilities associated with immune cells, namely (1) migration/invasion, which refers to the ability to move toward target cancer cells, (2) injury, which denotes the capacity to attack cancer cells, and (3) proliferation, which pertains to the ability of cells to multiply themselves.
This project aims to enhance immune cell function to treat solid tumors. To achieve this aim, I have developed a groundbreaking device capable of isolating cells that exhibit variations in these three capacities. Moreover, I have successfully validated the efficacy of the technology in isolating immune cells with diverse abilities by utilizing actual cancer cells.

Academic Significance and Societal Importance of the Research Achievements

本研究では独自に研究代表者らが開発した3つの新規技術「マイクロ流体デバイスを用いた運動機能による細胞選別方法」、T細胞と腫瘍組織との相互作用がin vitroでイメージング可能な「Tumor-on-a-chip」、「iPS細胞由来CAR-T細胞(CAR-iPS-T細胞)作製技術」をツールとして用いることにより、固形がんにおけるT細胞の遊走能力や浸潤能力の制御メカニズムの解明に取り組む。今回、免疫細胞を標的細胞への遊走性で選り分けることのできるこれまでにないデバイスの開発に成功した。これにより選別された免疫細胞を用いて、抗腫瘍効果に影響を及ぼす因子のスクリーニングができる可能性を拓いた。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (8 results)

All 2023 2022 2021 2020

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] がん免疫細胞療法のT細胞評価を可能とするチップ技術の開発2023

    • Author(s)
      三嶋雄太
    • Journal Title

      真の実臨床応用をめざした再生医療2023

      Volume: 41巻2号 Pages: 94-100

    • Related Report
      2022 Annual Research Report
  • [Journal Article] iPS細胞を用いた3次元がんチップの開発2022

    • Author(s)
      三嶋雄太
    • Journal Title

      Medical Science Digest

      Volume: 48巻13号 Pages: 51-53

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Suppression of multiple anti‐apoptotic BCL2 family proteins recapitulates the effects of JAK2 inhibitors in JAK2V617F driven myeloproliferative neoplasms2021

    • Author(s)
      Takei Hisashi、Coelho‐Silva Juan Luiz、Tavares Leal Cristina、Queiroz Arantes Rocha Adriana、Mantello Bianco Thiago、Welner Robert S.、Mishima Yuta、Kobayashi Ikei S.、Mullally Ann、Lima Keli、Machado‐Neto Joao Agostinho、Kobayashi Susumu S.、Lobo de Figueiredo‐Pontes Lorena
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 2 Pages: 597-608

    • DOI

      10.1111/cas.15210

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy2021

    • Author(s)
      Iriguchi Shoichi、Yasui Yutaka、Kawai Yohei、Arima Suguru、Kunitomo Mihoko、Sato Takayuki、Ueda Tatsuki、Minagawa Atsutaka、Mishima Yuta、Yanagawa Nariaki、Baba Yuji、Miyake Yasuyuki、Nakayama Kazuhide、Takiguchi Maiko、Shinohara Tokuyuki、Nakatsura Tetsuya、Yasukawa Masaki、Kassai Yoshiaki、Hayashi Akira、Kaneko Shin
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 430-430

    • DOI

      10.1038/s41467-020-20658-3

    • NAID

      120006954089

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of GM-CSF-producing antigen-presenting cells that induce a cytotoxic T cell-mediated antitumor response.2020

    • Author(s)
      Mashima H, Zhang R, Kobayashi T, Hagiya Y, Tsukamoto H, Liu T, Iwama T, Yamamoto M, Lin C, Nakatsuka R, Mishima Y, Watanabe N, Yamada T, Senju S, Kaneko S, Idiris A, Nakatsura T, Ohdan H, Uemura Y.
    • Journal Title

      Oncoimmunology

      Volume: 9(1) Issue: 1 Pages: 1814620-1814620

    • DOI

      10.1080/2162402x.2020.1814620

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Modeling of Tumor-on-a-Chip using HLA edited iPS cell-derived vascular endothelial cells for cancer immune cell therapy2021

    • Author(s)
      ○Yuta Mishima, Shin Kaneko and Yu-suke Torisawa
    • Organizer
      第80回 日本癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] がん免疫細胞療法の評価を目的としてiPS細胞由来血管内皮細胞を用いたTumor-on-a-Chipの開発2021

    • Author(s)
      ○三嶋 雄太、早稲田 真澄、高久保 瞳、森 千寿、佐野 絵美、王 博、上田 樹、金子 新、鳥澤 勇介
    • Organizer
      第20回 日本再生医療学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] MODELING CANCER IMMUNOTHERAPY IN A PERFUSABLE 3D VASCULARIZED TUMOR-ON-A-CHIP USING HLA-KO UNIVERSAL HUMAN IPSC-DERIVED ENDOTHELIAL CELLS2020

    • Author(s)
      ○Yuta Mishima, Masazumi Waseda, Hitomi Takakubo, Chihiro Mori, Emi Sano, Wang Bo, Tatsuki Ueda, Shoichi Iriguchi, Yuka Ozaki, Shin Kaneko, Yu-suke Torisawa
    • Organizer
      ISSCR 2020 Virtual
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2024-01-30  

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