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Efficacy of iPSC-derived chimeric antigen receptor T cell therapy for cervical cancer

Research Project

Project/Area Number 21K07249
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionJuntendo University

Principal Investigator

Ando Jun  順天堂大学, 医学部, 教授 (60348943)

Co-Investigator(Kenkyū-buntansha) 安藤 美樹  順天堂大学, 医学部, 教授 (10424251)
寺尾 泰久  順天堂大学, 医学部, 教授 (00348997)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsキメラ抗原受容体T細胞療法 / B7-H3 / 子宮頸がん / iPS細胞技術 / CAR-T療法 / 免疫細胞療法 / iPS細胞由来T細胞 / 難治性子宮頸がん / ヒトパピローマウイルス特異的CTL / iPS細胞
Outline of Research at the Start

子宮頸がんの若年層における罹患数は増加しているが、進行期では根治が望めず極めて予後不良である。近年、キメラ抗原受容体T細胞療法(CART療法)の開発が進んでいるが、子宮頸がんに対する有望なCART療法は未だない。本研究では難治性の子宮頸がんに対し、iPSC技術を用いた有効なCART療法を開発するための基礎研究を行う。最初に子宮頸がんに発現している表面抗原を解析して、良い標的抗原を探索する。その抗原に対するCARを作製してCART療法の有効性を検証する。更にiPSC技術を用いることで、より強く持続的な抗腫瘍効果を発揮できるかどうか詳細な検討を行う。

Outline of Final Research Achievements

Cervical cancer is increasing in the young generation and with those found in the advanced stages, complete cure is difficult to achieve and therefore their prognosis is extremely poor. CD19-CART therapy for Acute lymphocytic leukemia (ALL) and lymphoma has already been successfully applied. CART therapy for solid tumor is also progressing, but there is still no promising CART therapy for cervical cancer. We confirmed that cervical cancer cell lines are strongly positive for B7-H3 (CD276). In this study, using the iPS cell technology that we have developed so far, we will conduct basic studies aimed at developing effective and powerful CART therapy targeting B7-H3 in cervical cancer cells.

Academic Significance and Societal Importance of the Research Achievements

子宮頸がんの限局期には手術や放射線治療、化学療法が選択されるが、進行期では根治が望めず極めて予後不良である。特に手術や放射線治療、化学療法後の再発・難治性の子宮頸がん患者には手立てがなく、新規治療開発が喫緊の課題である。われわれの開発するCART療法が新規治療につながる可能性があるので、学術的に重要な検討であり意義があると思われる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021 Other

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (6 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] iPSC-derived hypoimmunogenic tissue resident memory T-cells mediate robust anti-tumor activity against cervical cancer2023

    • Author(s)
      Furukawa Yoshiki、Ishii Midori、Ando Jun、Ikeda Kazuya、Igarashi Kyomi J.、Kinoshita Shintaro、Azusawa Yoko、Toyota Tokuko、Honda Tadahiro、Nakanishi Mahito、Ohshima Koichi、Masuda Ayako、Yoshida Emiko、Kitade Mari、Porteus Matthew、Terao Yasuhisa、Nakauchi Hiromitsu、Ando Miki
    • Journal Title

      Cell Reports Medicine

      Volume: 4 Issue: 12 Pages: 101327-101327

    • DOI

      10.1016/j.xcrm.2023.101327

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Advances in Allogeneic Cancer Cell Therapy and Future Perspectives on “Off-the-Shelf” T Cell Therapy Using iPSC Technology and Gene Editing2022

    • Author(s)
      Furukawa Yoshiki、Hamano Yasuharu、Shirane Shuichi、Kinoshita Shintaro、Azusawa Yoko、Ando Jun、Nakauchi Hiromitsu、Ando Miki
    • Journal Title

      Cells

      Volume: 11 Issue: 2 Pages: 269-269

    • DOI

      10.3390/cells11020269

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dual-antigen targeted iPSC-derived chimeric antigen receptor-T cell therapy for refractory lymphoma2022

    • Author(s)
      Harada Sakiko、Ando Miki、Ando Jun、Ishii Midori、Yamaguchi Tomoyuki、Yamazaki Satoshi、Toyota Tokuko、Ohara Kazuo、Ohtaka Manami、Nakanishi Mahito、Shin Chansu、Ota Yasunori、Nakashima Kazutaka、Ohshima Koichi、Imai Chihaya、Nakazawa Yozo、Nakauchi Hiromitsu、Komatsu Norio
    • Journal Title

      Molecular Therapy

      Volume: 30 Issue: 2 Pages: 534-549

    • DOI

      10.1016/j.ymthe.2021.10.006

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] iPSC-Derived Neoantigen-Specific CTL Therapy for Ewing Sarcoma2021

    • Author(s)
      Ishii Midori、Ando Jun、Yamazaki Satoshi、Toyota Tokuko、Ohara Kazuo、Furukawa Yoshiki、Suehara Yoshiyuki、Nakanishi Mahito、Nakashima Kazutaka、Ohshima Koichi、Nakauchi Hiromitsu、Ando Miki
    • Journal Title

      Cancer Immunology Research

      Volume: 9 Issue: 10 Pages: 1175-1186

    • DOI

      10.1158/2326-6066.cir-21-0193

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SCLC-J1, a novel small cell lung cancer cell line2021

    • Author(s)
      Ohara Kazuo、Kinoshita Shintaro、Ando Jun、Azusawa Yoko、Ishii Midori、Harada Sakiko、Mitsuishi Yoichiro、Asao Tetsuhiko、Tajima Ken、Yamamoto Taketsugu、Takahashi Fumiyuki、Komatsu Norio、Takahashi Kazuhisa、Ando Miki
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 27 Pages: 101089-101089

    • DOI

      10.1016/j.bbrep.2021.101089

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trigenic ADH5/ALDH2/ADGRV1 mutations in myelodysplasia with Usher syndrome2021

    • Author(s)
      Kinoshita Shintaro、Ando Miki、Ando Jun、Ishii Midori、Furukawa Yoshiki、Tomita Osamu、Azusawa Yoko、Shirane Shuichi、Kishita Yoshihito、Yatsuka Yukiko、Eguchi Hidetaka、Okazaki Yasushi、Komatsu Norio
    • Journal Title

      Heliyon

      Volume: 7 Issue: 8 Pages: e07804-e07804

    • DOI

      10.1016/j.heliyon.2021.e07804

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] CAR-T 療法の経験とより良い治療成績への取り組み2023

    • Author(s)
      安藤純
    • Organizer
      第71回日本輸血・細胞治療学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Ewing肉腫のネオアンチゲンを標的とするiPSC由来細胞傷害性T細胞の抗腫瘍効果の検討2021

    • Author(s)
      63.石井翠、安藤美樹、豊田釈子、小原和男、末原義之、安藤純、小松則夫、中内啓光
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 難治性リンパ腫に対する2抗原を標的とするiPSC由来T細胞療法の開発2021

    • Author(s)
      64.木下慎太郎、安藤美樹、原田早希子、石井翠、小原和男、豊田釈子、安藤純、小松則夫、中内啓光
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 成人T細胞白血病/リンパ腫に対するiPS細胞由来Tax抗原特異的CTL療法の開発2021

    • Author(s)
      66.杉本和也、安藤美樹、安藤純、石井翠、梓澤陽子、古川芳樹、木下 慎太郎、本田匡宏、原田早希子、中内啓光、小松則夫
    • Organizer
      第13回日本血液疾患免疫療法学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Trigenic ADH5 / ALDH2 / ADGRV1 mutations in myelodysplasia with Usher syndrome2021

    • Author(s)
      67.Shintaro Kinoshita,Miki Ando,Jun Ando,Midori Ishii,Yoshiki Furukawa,Osamu Tomita,Shuichi Shirane,Yoshihito Kishita,Yukiko Yatsuka, Hidetaka Eguchi, Yasushi Okazaki, Norio Komatsu
    • Organizer
      第83回日本血液学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Development of iPSC-derived Tax-specific CTL therapy for adult T-cell leukemia/lymphoma2021

    • Author(s)
      68.Kazuya Sugimoto, Miki Ando,Jun Ando,Midori Ishii,Yoko Azusawa, Yoshiki Furukawa,Shintaro Kinoshita, Tadahiro Honda, Sakiko Harada, Hiromitsu Nakauchi, Norio Komatsu
    • Organizer
      第83回日本血液学会学術集会
    • Related Report
      2021 Research-status Report
  • [Remarks] iPS細胞由来レジデントメモリーT細胞で子宮頸がん治療 健常人由来 ゲノム編集技術で拒絶反応軽減

    • URL

      https://www.juntendo.ac.jp/news/16776.html

    • Related Report
      2023 Annual Research Report
  • [Patent(Industrial Property Rights)] HPV特異的細胞傷害性Tリンパ球のT細胞受容体又はその機能的断片2023

    • Inventor(s)
      安藤美樹、石井翠、安藤純、中内啓光
    • Industrial Property Rights Holder
      学校法人 順天堂
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2023 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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