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In Vitro Generation of Stem Cell Memory-Like T Cells from Activated T Cells

  • Makoto Ando
  • Mari Ikeda
  • Akihiko YoshimuraEmail author
  • Taisuke Kondo
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2111)

Abstract

Adoptive T-cell therapy is an attractive strategy for cancer immunotherapy. The transfer of in vitro expanded tumor-associated antigen (TAA)-specific T cells from patients may effectively fight against the original tumor cells. The chimeric antigen receptor-engineered T (CAR-T) cells are also shown to be a promising therapy for hematologic malignancies. However, one of the limitations of these T-cell-based therapies is a rapid acquisition of tolerant (anergy, deletion, dysfunctional and/or exhausted) phenotypes of T cells during activation in vitro and/or after transfer in vivo. We and others found that stem cell memory T (TSCM) cells are strongly resistant against such tolerance, showing strong expansion and persistence in vivo, and provide long-lasting antitumor effects. Here we describe a protocol for the generation of phenotypically TSCM-like cells (iTSCM cells), which can be induced by simple co-culture of activated T cells with OP9 stroma cells expressing a Notch ligand. We also showed the methods of cancer immunotherapy by using NSG mice.

Key words

Adoptive T-cell therapy Stem cell memory T cells Notch signaling Co-culture with feeder cells EB virus-specific T cells NSG mice 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Makoto Ando
    • 1
  • Mari Ikeda
    • 1
  • Akihiko Yoshimura
    • 1
    Email author
  • Taisuke Kondo
    • 1
  1. 1.Department of Microbiology and ImmunologyKeio University School of MedicineShinjuku-kuJapan

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