Generation and Application of Stem Cell Memory T Cells
Project/Area Number |
16K15292
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Immunology
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Research Institution | Keio University |
Principal Investigator |
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Research Collaborator |
KONDO Taisuke
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 腫瘍免疫 / メモリーT細胞 / 疲弊化 / Notch / 分化制御 / 細胞移入療法 / 幹細胞メモリーT細胞 / 記憶T細胞 / 免疫学 / 代謝 / Notchシグナル / 抗腫瘍免疫 / 獲得免疫 / 細胞老化 / リプログラム / 癌 / シグナル伝達 |
Outline of Final Research Achievements |
A novel memory T cell subset, stem cell memory T (Tscm) cell, was recently discovered and is believed to be a useful tool for new T cell transfer therapy. Since Tscm cells are long-lived, and proliferate rapidly in response to antigenic stimulation to produce large numbers of effector T cells. We amplified EB virus and tumor antigen-specific T cells from human peripheral blood and co-cultured with human Notch-ligand and OP9 cells expressing hDLL1. This procedure converted effector T cells into Tscm-like cells (iTscm). We showed that iTscm cells have shown much more potent anti-tumor activity than conventional activated T cells in a humanized mouse model.
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Academic Significance and Societal Importance of the Research Achievements |
試験管内におけるTscm細胞の作製法およびがん免疫療法への応用が多数報告されている。しかしながら既報の作製法はナイーブT細胞に弱いTCR刺激やシグナル阻害剤を用いることで活性化を抑制しながら分化を誘導するものである。我々が開発したiTscm細胞は一旦活性化して疲弊化したT細胞からも作成できるところが特徴である。すなわち分化段階を一段巻き戻したものであり、このメカニズムを解明する事でいまだ十分解明されていないTscmの発生機構が明らかになると思われる。また我々の方法はがんのT細胞移入療法の効果を高めうると考えられる。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy2017
Author(s)
Taisuke Kondo, Rimpei Morita, Yuumi Okuzono, Hiroko Nakatsukasa, Takashi Sekiya, Shunsuke Chikuma, Takashi Shichita, Mitsuhiro Kanamori, Masato Kubo, Keiko Koga, Takahiro Miyazaki, Yoshiaki Kassai, Akihiko Yohimura
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Journal Title
Nature Communications
Volume: 8
Issue: 1
Pages: 15338-15338
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy2017
Author(s)
Taisuke Kondo, Rimpei Morita, Yuumi Okuzono, Hiroko Nakatsukasa, Takashi Sekiya, Shunsuke Chikuma, Takashi Shichita, Mitsuhiro Kanamori, Masato Kubo, Keiko Koga, Takahiro Miyazaki, Yoshiaki Kassai, Yoshimura Akihiko
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Journal Title
Nature Communications
Volume: 印刷中
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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