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<p>T cell exhaustion remains a critical barrier in treating chronic infections and cancer. To overcome this, our laboratory has established a platform for generating “rejuvenated” T cells from induced pluripotent stem cells (iPSCs). This review outlines our research trajectory, transitioning from the foundational autologous “T-iPSC” concept to scalable, “off-the-shelf” allogeneic strategies. We detail the establishment of clinical-grade, xeno-free manufacturing protocols and the integration of advanced gene editing—including functional enhancement through intracellular signaling modulation, immune rejection–related gene editing to minimize immunogenicity, and optimization of synthetic receptor architectures to mitigate the risk of Graft-versus-Host Disease (GvHD) while enhancing targeting efficiency. Furthermore, we describe our activity on generating regulatory T cells from iPSC for managing autoimmune disorders and GvHD. Finally, we discuss the remaining challenges and the future roadmap for translating these therapeutic T cells into clinical practice.</p>

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Generation of therapeutic T cells from human induced pluripotent stem cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月30日

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  • Bo Wang,
  • Shin Kaneko

摘要

T cell exhaustion remains a critical barrier in treating chronic infections and cancer. To overcome this, our laboratory has established a platform for generating “rejuvenated” T cells from induced pluripotent stem cells (iPSCs). This review outlines our research trajectory, transitioning from the foundational autologous “T-iPSC” concept to scalable, “off-the-shelf” allogeneic strategies. We detail the establishment of clinical-grade, xeno-free manufacturing protocols and the integration of advanced gene editing—including functional enhancement through intracellular signaling modulation, immune rejection–related gene editing to minimize immunogenicity, and optimization of synthetic receptor architectures to mitigate the risk of Graft-versus-Host Disease (GvHD) while enhancing targeting efficiency. Furthermore, we describe our activity on generating regulatory T cells from iPSC for managing autoimmune disorders and GvHD. Finally, we discuss the remaining challenges and the future roadmap for translating these therapeutic T cells into clinical practice.