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

Department of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

76 Citations (Scopus)

Abstract

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.

Original language	English
Article number	15338
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15338
Publication status	Published - 2017 May 22

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

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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

Abstract

ASJC Scopus subject areas

UN SDGs

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