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The development of immune cell therapy using iPSC-derived T cells targeting refractory cervical cancers

Research Project

Project/Area Number 18K07273
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) 寺尾 泰久  順天堂大学, 医学部, 教授 (00348997)
安藤 美樹  順天堂大学, 医学部, 教授 (10424251)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords子宮頸がん / 免疫細胞療法 / iPS技術 / ヒト・パピローマウイルス特異的細胞傷害性T細胞 / 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
Outline of Final Research Achievements

We reprogrammed human papilloma virus (HPV)-specific CTLs by Sendai virus vector. The iPSCs efficiently differentiated into HPV-specific rejuvenated CTLs that demonstrated robust cytotoxicity against cervical cancer. The tumor-suppressive effect of rejuvenated CTLs was stronger and more persistent than that of original peripheral blood CTLs. These rejuvenated HPV-specific CTLs provide a sustained tumor-suppressive effect and constitute promising immunotherapy for cervical cancer.

Academic Significance and Societal Importance of the Research Achievements

iPS技術を用いた免疫細胞療法には大きな可能性がある。子宮頸がんの進行期や再発した症例では、根治的手術や放射線治療の適応とならず、根治は望めず予後不良である。そのため新たな治療戦略が求められている。本研究は健常人ドナーの末梢血からT細胞を誘導し、iPS技術を用いて若返りT細胞を作製しin vitroとin vivoで抗腫瘍効果を証明した。 iPS細胞からT細胞へ分化誘導したT細胞は、腫瘍を継続的に根絶し、in vivoで若いメモリーT細胞として長期間生存することが出来た。これらの若返ったT細胞は、持続的な腫瘍抑制効果を認め、将来的に子宮頸癌に対する有望な免疫細胞療法となる可能性がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (17 results)

All 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (11 results) (of which Int'l Joint Research: 1 results)

  • [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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vitamin B6 deficiency is prevalent in primary and secondary myelofibrosis patients2019

    • Author(s)
      Yasuda Hajime、Tsutsui Miyuki、Ando Jun、Inano Tadaaki、Noguchi Masaaki、Yahata Yuriko、Tanaka Masaru、Tsukune Yutaka、Masuda Azuchi、Shirane Shuichi、Misawa Kyohei、Gotoh Akihiko、Sato Eriko、Aritaka Nanae、Sekiguchi Yasunobu、Sugimoto Keiji、Komatsu Norio
    • Journal Title

      International Journal of Hematology

      Volume: 110 Issue: 5 Pages: 543-549

    • DOI

      10.1007/s12185-019-02717-8

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multiple Placental Infarcts in a Pregnant Woman with Essential Thrombocythemia2018

    • Author(s)
      Edahiro Yoko、Ando Jun、Suzuki Toshifumi、Fukumura Yuki、Masuda Azuchi、Sakayori Shiori、Takeda Jun、Maruyama Yojiro、Makino Shintaro、Itakura Atsuo、Komatsu Norio
    • Journal Title

      Internal Medicine

      Volume: 57 Issue: 24 Pages: 3647-3650

    • DOI

      10.2169/internalmedicine.1311-18

    • NAID

      130007531198

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recurrent amylase-producing multiple myeloma responding to pomalidomide and carfilzomib-containing therapies2018

    • Author(s)
      青田 泰雄、後藤 明彦、奥田 優子、本田 匡宏、渡辺 直紀、安藤 純、小松 則夫
    • Journal Title

      Rinsho Ketsueki

      Volume: 59 Issue: 7 Pages: 865-871

    • DOI

      10.11406/rinketsu.59.865

    • NAID

      130007430655

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [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] 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] 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] The Preclinical Study of iPSC-derived CTL Therapy for EBV-associated Lymphoma2018

    • Author(s)
      Miki Ando, Jun Ando, Midori Ishii, Yumi Sakiyama, Sakiko Harada, Tadahiro Honda, Masako Fujita, Norio Komatsu, and Hiromitsu Nakauchi
    • Organizer
      ISSCR 2018 Annual Meeting(国際学会)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [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2018

    • 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10回血液疾患免疫療法学会学術集会
    • Related Report
      2018 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2018

    • Author(s)
      安藤美樹、安藤純、石井翠、原田早希子、本田匡宏、藤田雅子、中内啓光、小松則夫
    • Organizer
      第10回血液疾患免疫療法学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] The role of CD8β-chain in iPSC-derived rejuvenated CTL therapy2018

    • Author(s)
      本田匡宏、安藤美樹、崎山祐未、村越勇人、安藤純、滝口雅文、中内啓光、小松則夫
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 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2018

    • 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18回日本再生医療学会総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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