3 years ago

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

Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy
Mitsuhiro Kanamori, Takashi Sekiya, Taisuke Kondo, Takashi Shichita, Yuumi Okuzono, Takahiro Miyazaki, Masato Kubo, Yoshiaki Kassai, Shunsuke Chikuma, Keiko Koga, Akihiko Yoshimura, Rimpei Morita, Hiroko Nakatsukasa
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.

Publisher URL: http://www.nature.com/articles/ncomms15338

DOI: 10.1038/ncomms15338

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