Laboratory of Immunology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Laboratory of Regenerative Immunology, International Center for Cell and Gene Therapy, Fujita Health University, Toyoake, Japan.
Adv Exp Med Biol. 2024;1444:207-217. doi: 10.1007/978-981-99-9781-7_14.
In the field of cancer immunotherapy, the effectiveness of a method in which patient-derived T cells are genetically modified ex vivo and administered to patients has been demonstrated. However, problems remain with this method, such as (1) time-consuming, (2) costly, and (3) difficult to guarantee the quality. To overcome these barriers, strategies to regenerate T cells using iPSC technology are being pursued by several groups in the last decade. The authors have been developing a method by which specific TCR genes are introduced into iPSCs and T cells are generated from those iPSCs (TCR-iPSC method). At present, our group is preparing this approach for clinical trial, where iPSCs provided from the iPSC project are transduced with WT1 antigen-specific TCR that had been already clinically tested, and killer T cells are generated from such TCR-iPSCs, to be administered to acute myeloid leukemia patients. While the adoptive T cell therapies have been mainly directed to be used in cancer immunotherapy, it is possible to apply these approaches to viral infections. Strategies by other groups to regenerate various types of T cells from iPSCs will also be introduced.
在癌症免疫疗法领域，已经证明了一种方法的有效性，即将患者来源的 T 细胞进行体外基因修饰并回输给患者。然而，这种方法仍然存在一些问题，例如（1）耗时，（2）昂贵，（3）难以保证质量。为了克服这些障碍，过去十年中，许多研究小组都在寻求使用 iPSC 技术再生 T 细胞的策略。作者一直在开发一种方法，即将特定的 TCR 基因引入 iPSC，并从这些 iPSC 中生成 T 细胞（TCR-iPSC 方法）。目前，我们小组正在为临床试验做准备，从 iPSC 项目中提供的 iPSC 被已经经过临床测试的 WT1 抗原特异性 TCR 转导，并且从这些 TCR-iPSC 中生成杀伤性 T 细胞，然后将其施用于急性髓细胞性白血病患者。虽然过继性 T 细胞疗法主要用于癌症免疫疗法，但也可以将这些方法应用于病毒感染。其他小组从 iPSC 再生各种类型 T 细胞的策略也将被介绍。
