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The efficacy and safety of iPSC-derived CART therapy for small cell lung cancer

Research Project

Project/Area Number 19K07781
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 Miki  順天堂大学, 医学部, 教授 (10424251)

Co-Investigator(Kenkyū-buntansha) 安藤 純  順天堂大学, 医学部, 教授 (60348943)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsキメラ抗原受容体T細胞 / 小細胞肺がん / GD2-CAR / T-iPSC / 若返りCTL / T-iPS
Outline of Research at the Start

本研究では小細胞肺がんの多くが細胞表面に糖鎖抗原であるGD2を発現することに着目し、先行技術の応用によりiPS細胞にGD2-CARを遺伝子導入後、若返りGD2-CARTを分化誘導し、小細胞肺がんに強力な治療となりうるか検証する。また、副作用発現時もしくはCARTが不要になった場合に体内から消失できるよう、自殺遺伝子細胞死誘導システムを備え、安全性と有効性の両方を担保できる画期的な治療の基礎開発を行う。

Outline of Final Research Achievements

We have reported that iPSC-derived dual-antigen receptor rejuvenated T cells (rejTs) can target CD19 antigen via chimeric antigen receptor (CAR) and Epstein-Barr LMP2 antigen via native TCR, resulting in robust anti-tumor effect against EBV-associated lymphoma (Harada et al., Molecular Therapy, 2021). Applying this strategy to GD2 positive refractory tumors, we generated iPSC-derived GD2-CAR-rejTs and examined the efficacy and safety against GD2-positive small cell lung cancer (SCLC). Peripheral blood-derived GD2-CARTs did not show cytotoxicity against SCLC cell lines, whereas GD2-CAR-rejTs showed much stronger cytotoxicity against SCLC cell lines than that of peripheral blood-derived GD2-CARTs in vitro. Furthermore, GD2-CAR-rejTs successfully suppressed tumor growth in vivo compared to untreated mice. This approach would be a promising therapy for refractory SCLC.

Academic Significance and Societal Importance of the Research Achievements

小細胞肺がんは肺がんの中で最も進行が速く、多くの患者は再発し治療抵抗性を示す。5年生存率は7%以下と極めて予後不良にも関わらず、新規治療開発から長らく取り残されてきた。本研究では小細胞肺がんの多くが細胞表面にGD2を発現することに着目し、iPSCにGD2-CARを遺伝子導入後GD2-CARTを分化誘導し、小細胞肺がんに強力な治療となりうるか検証した。末梢血GD2-CARTは小細胞肺がんに細胞傷害活性を示さなかったが、iPSC由来GD2-CARTは強い細胞傷害活性を示した。小細胞肺がんに対する新規治療となりうる有望な結果であり、その抗腫瘍効果の差について解析することも学問的に重要と考える。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (29 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 8 results) Book (2 results) Remarks (1 results)

  • [Int'l Joint Research] ベイラー医科大学/Stanford大学(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Century Therapeutics(米国)

    • Related Report
      2020 Research-status Report
  • [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
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2021 Annual Research 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 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term eradication of extranodal natural killer/T-cell lymphoma, nasal type, by induced pluripotent stem cell-derived Epstein-Barr virus-specific rejuvenated T cells in vivo2020

    • Author(s)
      Ando M, Ando J, Yamazaki S, Ishii M, Sakiyama Y, Harada S, Honda T, Yamaguchi T, Nojima M, Ohshima K, Nakauchi H, Komatsu N
    • Journal Title

      Haematologica

      Volume: 105 Issue: 3 Pages: 796-807

    • DOI

      10.3324/haematol.2019.223511

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of protective T-cell antigens for smallpox vaccines2020

    • Author(s)
      Ando Jun、Ngo Minhtran C.、Ando Miki、Leen Ann、Rooney Cliona M.
    • Journal Title

      Cytotherapy

      Volume: - Issue: 11 Pages: 642-652

    • DOI

      10.1016/j.jcyt.2020.04.098

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] iPSC-derived Rejuvenated T-cell Therapy for Extranodal NK/T-cell Lymphoma, Nasal Type2020

    • Author(s)
      Miki Ando, Jun Ando, Tadahiro Honda, Midori Ishii, Hiromitsu Nakauchi, and Norio Komatsu
    • Journal Title

      Juntendo Medical Journal

      Volume: 66 Issue: 3 Pages: 200-205

    • DOI

      10.14789/jmj.2020.66.JMJ20-R03

    • NAID

      130007867027

    • ISSN
      2187-9737, 2188-2126
    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sustainable tumor suppressive effect of iPSC-derived rejuvenated T cells targeting cervical cancers.2020

    • Author(s)
      Tadahiro Honda, Miki Ando, Jun Ando, Midori Ishii, Yumi Sakiyama, Kazuo Ohara, Tokuko Toyota, Manami Ohtaka, Ayako Masuda, Yasuhisa Terao, Mahito Nakanishi, Hiromitsu Nakauchi, and Norio Komatsu
    • Journal Title

      Molecular Therapy

      Volume: 28 Issue: 11 Pages: 2394-2405

    • DOI

      10.1016/j.ymthe.2020.07.004

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 難治性がんを標的にしたiPSC由来T細胞療法の開発2021

    • Author(s)
      安藤美樹
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Invited
  • [Presentation] Dual-antigen targeted iPSC-derived chimeric antigen receptor-T cell therapy for refractory lymphomas.2020

    • Author(s)
      Midori Ishii, Miki Ando, Sakiko Harada, Jun Ando, Tokuko Toyota, Norio Komatsu, and Hiromitsu Nakauchi
    • Organizer
      ISSCR 2020 Annual Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of iPSC-derived extended CTL therapy for cervical cancer2020

    • Author(s)
      Miki Ando, Jun Ando, Midori Ishii, Kazuo Ohara, Tokuko Toyota, Risa Matsuoka, Mari Kitade, Yasuhisa Terao, Norio Komatsu and Hiromitsu Nakauchi
    • Organizer
      ISSCR 2020 Annual Meeting
    • Related Report
      2020 Research-status Report
  • [Presentation] 難治性がんに対する“off-the-shelf”T細胞療法の実現2020

    • Author(s)
      安藤美樹
    • Organizer
      第109回未来医療セミナー
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 子宮頸がんに対する持続可能なiPSC由来CTL療法の開発2020

    • Author(s)
      安藤美樹
    • Organizer
      令和2年度AMED再生・細胞医療・遺伝子治療交流会・シンポジウム、遺伝子改変細胞
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] iPS技術を用いた難治性がんに対する若返りT細胞療法の開発2019

    • Author(s)
      安藤美樹
    • Organizer
      第348回順天堂医学会学術集会 医学研究のUP-TO DATE
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] EBウイルス関連リンパ腫に対するiPS細胞由来若返りCTL療法の前臨床試験2019

    • Author(s)
      安藤美樹
    • Organizer
      第29回日本サイトメトリー学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] EBウイルス関連リンパ腫に対するiPSC由来若返りCTL療法の前臨床試験~ First In Human を目指す私たちの試み~2019

    • Author(s)
      安藤美樹
    • Organizer
      第59回日本リンパ網内系学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 難治性EBウイルス関連リンパ腫に対するiPS細胞由来LMP1-CART療法の開発2019

    • Author(s)
      原田早希子、安藤美樹、山口智之、安藤純、中沢洋三、中内啓光、小松則夫
    • Organizer
      第11回血液疾患免疫療法学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Ewing肉腫のネオアンチゲンを標的とするiPS細胞由来細胞傷害性T細胞療法の開発2019

    • Author(s)
      石井翠、安藤美樹、原田早希子、本田匡宏、末原義之、安藤純、小松則夫、中内啓光
    • Organizer
      第11回血液疾患免疫療法学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 子宮頸がんに対するiPS細胞由来CTL療法の開発2019

    • Author(s)
      本田匡宏、安藤美樹、安藤純、崎山祐未、中内啓光、小松則夫
    • Organizer
      第11回血液疾患免疫療法学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] iPSC-derived CTL therapy for cervical cancer by targeting human papillomavirus (HPV)2019

    • Author(s)
      Tadahiro Honda,Miki Ando,Yumi Sakiyama,Midori Ishii,Sakiko Harada,Kazuo Ohara,Jun Ando,Hiromitsu Nakauchi,Norio Komatsu
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] The neoantigen-specific iPSC-derived rejuvenated CTL therapy for Ewing sarcoma2019

    • Author(s)
      Midori Ishii,Miki Ando,Yumi Sakiyama,Sakiko Harada,Tadahiro Honda,Jun Ando,Norio Komatsu,Hiromitsu Nakauchi
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Development of iPS cell derived LMP1-CART therapy for refractory EB virus associated lymphomas2019

    • Author(s)
      Sakiko Harada,Miki Ando,Jun Ando,Satoshi Yamasaki,Midori Ishii,Tadahiro Honda,Kazuo Ohara,Yumi Sakiyama,Yozo Nakazawa,Malcolm K. Brenner,Hiromitsu Nakauchi,Norio Komatsu
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] EBウイルス関連リンパ腫に対するiPS細胞由来若返りCTL療法の前臨床試験2019

    • Author(s)
      安藤美樹
    • Organizer
      第8回日本免疫・細胞治療学会学術総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 子宮頸がんに対するiPS細胞を用いた”off-the-shelf”CTL療法2019

    • Author(s)
      安藤美樹
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Book] Improving the safety of iPSC-derived T cell therapy; Molecular Players in iPSC Technology2021

    • Author(s)
      Ando M, Kinoshita S, Furukawa Y, Ando J, Nakauchi H, Brenner MK
    • Total Pages
      21
    • Publisher
      Elsevier
    • Related Report
      2021 Annual Research Report
  • [Book] iPS細胞技術を用いる若返りT細胞療法の開発―実臨床に向けた開発戦略2020

    • Author(s)
      安藤美樹、中内啓光
    • Publisher
      実験医学増刊 羊土社
    • Related Report
      2020 Research-status Report 2019 Research-status Report
  • [Remarks] iPS細胞由来の免疫キラーT細胞を用いることで悪性リンパ腫の治癒に成功

    • URL

      https://www.juntendo.ac.jp/news/20190726-01.html

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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