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

Author

Listed:
  • 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
    Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences (IMS), RIKEN Yokohama Institute)

  • 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)

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.

Suggested Citation

  • Taisuke Kondo & Rimpei Morita & Yuumi Okuzono & Hiroko Nakatsukasa & Takashi Sekiya & Shunsuke Chikuma & Takashi Shichita & Mitsuhiro Kanamori & Masato Kubo & Keiko Koga & Takahiro Miyazaki & Yoshiaki, 2017. "Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15338
    DOI: 10.1038/ncomms15338
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