Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy

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 Yoshimura

doi:10.1038/ncomms15338

Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy

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 Yoshimura

研究成果: ジャーナルへの寄稿 › 学術誌 › 査読

76 被引用数 (Scopus)

抄録

Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (T_SCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8⁺ T_SCM cells can be generated in vitro from naive CD8⁺ T cells via Wnt signalling; however, methods do not yet exist for inducing T_SCM cells from activated or memory T cells. Here, we show a strategy for generating T_SCM -like cells in vitro (iT_SCM cells) from activated CD4⁺ and CD8⁺ T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iT_SCM cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy.

本文言語	英語
論文番号	15338
ジャーナル	Nature communications
巻	8
DOI	https://doi.org/10.1038/ncomms15338
出版ステータス	出版済み - 5月 22 2017
外部発表	はい

!!!All Science Journal Classification (ASJC) codes

一般
物理学および天文学（全般）
化学 (全般)
生化学、遺伝学、分子生物学（全般）

UN SDG

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title = "Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy",

abstract = "Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8+ TSCM cells can be generated in vitro from naive CD8+ T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM -like cells in vitro (iTSCM cells) from activated CD4+ and CD8+ T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iTSCM cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy.",

author = "Taisuke Kondo and Rimpei Morita and Yuumi Okuzono and Hiroko Nakatsukasa and Takashi Sekiya and Shunsuke Chikuma and Takashi Shichita and Mitsuhiro Kanamori and Masato Kubo and Keiko Koga and Takahiro Miyazaki and Yoshiaki Kassai and Akihiko Yoshimura",

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AU - Kondo, Taisuke

AU - Morita, Rimpei

AU - Okuzono, Yuumi

AU - Nakatsukasa, Hiroko

AU - Sekiya, Takashi

AU - Chikuma, Shunsuke

AU - Shichita, Takashi

AU - Kanamori, Mitsuhiro

AU - Kubo, Masato

AU - Koga, Keiko

AU - Miyazaki, Takahiro

AU - Kassai, Yoshiaki

AU - Yoshimura, Akihiko

PY - 2017/5/22

Y1 - 2017/5/22

N2 - Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8+ TSCM cells can be generated in vitro from naive CD8+ T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM -like cells in vitro (iTSCM cells) from activated CD4+ and CD8+ T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iTSCM cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy.

AB - Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8+ TSCM cells can be generated in vitro from naive CD8+ T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM -like cells in vitro (iTSCM cells) from activated CD4+ and CD8+ T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iTSCM cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy.

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Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy

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!!!All Science Journal Classification (ASJC) codes

UN SDG

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