Generation of therapeutic T cells from human induced pluripotent stem cells

Bo Wang1, Shin Kaneko2

  • 1Shin Kaneko Laboratory, Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan. wang.bo.3w@kyoto-u.ac.jp.

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.

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Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore called induced pluripotent stem...
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