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Nat Commun. 2017 May 22;8:15338. doi: 10.1038/ncomms15338.

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

Author information

1
Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
2
Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi 2-chome, Fujisawa-shi, Kanagawa 251-8555, Japan.
3
Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
4
Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences (IMS), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan.

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.

PMID:
28530241
PMCID:
PMC5458121
DOI:
10.1038/ncomms15338
[Indexed for MEDLINE]
Free PMC Article

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