Kawamoto Hiroshi, Kawase Takakazu, Nagano Seiji
Laboratory of Immunology, Institute for Life and Medical Sciences, Kyoto University.
Laboratory of Regenerative Immunology, International Center for Cell and Gene Therapy, Fujita Health University.
Rinsho Ketsueki. 2024;65(9):1075-1086. doi: 10.11406/rinketsu.65.1075.
Methods in which patient-derived T cells are genetically modified in vitro and administered to patients have been demonstrated effective in the area of cancer immunotherapy. However, these methods have some unresolved issues such as cost, time, and unstable quality. Several groups have developed strategies to overcome these barriers by regenerating T cells from iPSCs. We have been developing a method in which specific TCR genes are introduced into iPSCs and T cells are regenerated from these iPSCs (TCR-iPSC method). We are now using starting iPSCs from the iPSC stock lines provided by CiRA-F, as the iPSC stock cells are less likely to be rejected. A study aimed at application to solid tumors demonstrated the therapeutic effect of regenerated T cells in a patient tissue xenograft model of WT1 antigen-positive renal cell carcinoma. This article will also discuss strategies by other groups to regenerate various types of T cells from iPSCs.
在癌症免疫治疗领域，将患者来源的T细胞在体外进行基因改造后再给予患者的方法已被证明是有效的。然而，这些方法存在一些尚未解决的问题，如成本、时间和质量不稳定等。几个研究小组已经开发出通过诱导多能干细胞（iPSC）再生T细胞来克服这些障碍的策略。我们一直在开发一种方法，即将特定的T细胞受体（TCR）基因导入iPSC，并从这些iPSC再生T细胞（TCR-iPSC方法）。我们现在使用CiRA-F提供的iPSC细胞系中的起始iPSC，因为这些iPSC库存细胞不太可能被排斥。一项旨在应用于实体瘤的研究在WT1抗原阳性肾细胞癌的患者组织异种移植模型中证明了再生T细胞的治疗效果。本文还将讨论其他研究小组从iPSC再生各种类型T细胞的策略。
