Details

Autor(en) / Beteiligte

• Iriguchi, Shoichi
• Yasui, Yutaka
• Kawai, Yohei
• Arima, Suguru
• Kunitomo, Mihoko
• Sato, Takayuki
• Ueda, Tatsuki
• Minagawa, Atsutaka
• Mishima, Yuta
• Yanagawa, Nariaki
• Baba, Yuji
• Miyake, Yasuyuki
• Nakayama, Kazuhide
• Takiguchi, Maiko
• Shinohara, Tokuyuki
• Nakatsura, Tetsuya
• Yasukawa, Masaki
• Kassai, Yoshiaki
• Hayashi, Akira
• Kaneko, Shin

Titel

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

Ist Teil von

• Nature communications, 2021-01, Vol.12 (1), p.430-430, Article 430

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. T-cell immunotherapies, such as CAR-T immunotherapy, are being developed against a wide variety of diseases. Here the authors report the feeder-free, scalable differentiation of human induced pluripotent cells (iPSCs) to T-cells with T-cell receptor dependent anti-tumour function in vitro and in vivo.