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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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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, …
Nature Communications, 卷.8, 15338
05/2017
PMID: 28530241

摘要

Chemistry (all) Biochemistry Genetics and Molecular Biology (all) Multidisciplinary Physics and Astronomy (all)
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.

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https://doi.org/10.1038/ncomms15338檢視
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