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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.

SUBMITTER: Kondo T 

PROVIDER: S-EPMC5458121 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Kondo Taisuke T   Morita Rimpei R   Okuzono Yuumi Y   Nakatsukasa Hiroko H   Sekiya Takashi T   Chikuma Shunsuke S   Shichita Takashi T   Kanamori Mitsuhiro M   Kubo Masato M   Koga Keiko K   Miyazaki Takahiro T   Kassai Yoshiaki Y   Yoshimura Akihiko A  

Nature communications 20170522

Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (T<sub>SCM</sub>) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8<sup>+</sup> T<sub>SCM</sub> cells can be generated in vitro from naive CD8<sup>+</sup> T cells via Wnt signalling; however, methods do not yet exist for inducing T<sub>SCM</sub> cells from activated or memory T cells. Here, we show a strategy for generating T<sub>SCM</sub>-like cells in vitro (  ...[more]

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