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, Akihiko Yoshimura

Research output: Contribution to journalArticle

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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.

LanguageEnglish
Article number15338
JournalNature Communications
Volume8
DOIs
StatePublished - 2017 May 22

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Adoptive Immunotherapy
T-cells
stem cells
notches
Stem cells
Stem Cells
T-Lymphocytes
Data storage equipment
cells
effectors
antigens
Stromal Cells
Tumors
Immunotherapy
mice
therapy
Neoplasms
Ligands
tumors
Antigens

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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

In: Nature Communications, Vol. 8, 15338, 22.05.2017.

Research output: Contribution to journalArticle

Kondo, T, Morita, R, Okuzono, Y, Nakatsukasa, H, Sekiya, T, Chikuma, S, Shichita, T, Kanamori, M, Kubo, M, Koga, K, Miyazaki, T, Kassai, Y & Yoshimura, A 2017, 'Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy' Nature Communications, vol 8, 15338. DOI: 10.1038/ncomms15338
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. / Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy. In: Nature Communications. 2017 ; Vol. 8.
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AU - Sekiya,Takashi

AU - Chikuma,Shunsuke

AU - Shichita,Takashi

AU - Kanamori,Mitsuhiro

AU - Kubo,Masato

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