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 and Akihiko Yoshimura ()
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Taisuke Kondo: Keio University School of Medicine
Rimpei Morita: Keio University School of Medicine
Yuumi Okuzono: Inflammation Drug Discovery Unit, Takeda Pharmaceutical Company Limited
Hiroko Nakatsukasa: Keio University School of Medicine
Takashi Sekiya: Keio University School of Medicine
Shunsuke Chikuma: Keio University School of Medicine
Takashi Shichita: Keio University School of Medicine
Mitsuhiro Kanamori: Keio University School of Medicine
Masato Kubo: Research Institute for Biomedical Science, Tokyo University of Science
Keiko Koga: Inflammation Drug Discovery Unit, Takeda Pharmaceutical Company Limited
Takahiro Miyazaki: Inflammation Drug Discovery Unit, Takeda Pharmaceutical Company Limited
Yoshiaki Kassai: Inflammation Drug Discovery Unit, Takeda Pharmaceutical Company Limited
Akihiko Yoshimura: Keio University School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15338

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