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

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...

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Detalles Bibliográficos
Autores principales: Kondo, Taisuke, Morita, Rimpei, Okuzono, Yuumi, Nakatsukasa, Hiroko, Sekiya, Takashi, Chikuma, Shunsuke, Shichita, Takashi, Kanamori, Mitsuhiro, Kubo, Masato, Koga, Keiko, Miyazaki, Takahiro, Kassai, Yoshiaki, Yoshimura, Akihiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458121/
https://www.ncbi.nlm.nih.gov/pubmed/28530241
http://dx.doi.org/10.1038/ncomms15338
Descripción
Sumario: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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