A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy

Shoichi Iriguchi, Yutaka Yasui, Yohei Kawai, Suguru Arima, Mihoko Kunitomo, Takayuki Sato, Tatsuki Ueda, Atsutaka Minagawa, Yuta Mishima, Nariaki Yanagawa, Yuji Baba, Yasuyuki Miyake, Kazuhide Nakayama, Maiko Takiguchi, Tokuyuki Shinohara, Tetsuya Nakatsura, Masaki Yasukawa, Yoshiaki Kassai, Akira Hayashi and Shin Kaneko ()
Additional contact information
Shoichi Iriguchi: Kyoto University
Yutaka Yasui: Kyoto University
Yohei Kawai: Kyoto University
Suguru Arima: Takeda-CiRA Joint Program (T-CiRA)
Mihoko Kunitomo: Takeda-CiRA Joint Program (T-CiRA)
Takayuki Sato: Takeda-CiRA Joint Program (T-CiRA)
Tatsuki Ueda: Kyoto University
Atsutaka Minagawa: Kyoto University
Yuta Mishima: Kyoto University
Nariaki Yanagawa: Kyoto University
Yuji Baba: Takeda-CiRA Joint Program (T-CiRA)
Yasuyuki Miyake: Kyoto University
Kazuhide Nakayama: Takeda-CiRA Joint Program (T-CiRA)
Maiko Takiguchi: Takeda-CiRA Joint Program (T-CiRA)
Tokuyuki Shinohara: Takeda-CiRA Joint Program (T-CiRA)
Tetsuya Nakatsura: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center
Masaki Yasukawa: Ehime University Graduate School of Medicine
Yoshiaki Kassai: Takeda-CiRA Joint Program (T-CiRA)
Akira Hayashi: Takeda-CiRA Joint Program (T-CiRA)
Shin Kaneko: Kyoto University

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Clinical successes demonstrated by chimeric antigen receptor T-cell immunotherapy have facilitated further development of T-cell immunotherapy against wide variety of diseases. One approach is the development of “off-the-shelf” T-cell sources. Technologies to generate T-cells from pluripotent stem cells (PSCs) may offer platforms to produce “off-the-shelf” and synthetic allogeneic T-cells. However, low differentiation efficiency and poor scalability of current methods may compromise their utilities. Here we show improved differentiation efficiency of T-cells from induced PSCs (iPSCs) derived from an antigen-specific cytotoxic T-cell clone, or from T-cell receptor (TCR)-transduced iPSCs, as starting materials. We additionally describe feeder-free differentiation culture systems that span from iPSC maintenance to T-cell proliferation phases, enabling large-scale regenerated T-cell production. Moreover, simultaneous addition of SDF1α and a p38 inhibitor during T-cell differentiation enhances T-cell commitment. The regenerated T-cells show TCR-dependent functions in vitro and are capable of in vivo anti-tumor activity. This system provides a platform to generate a large number of regenerated T-cells for clinical application and investigate human T-cell differentiation and biology.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20658-3

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DOI: 10.1038/s41467-020-20658-3

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