Chimeric antigen receptor (CAR) T cell therapy is a promising cell-based immunotherapy applicable to various cancers. High cost of production, immune rejection, heterogeneity of cell product, limited cell source, limited expandability, and relatively long production time have created the need to achieve a universal allogeneic CAR-T cell product for "off-the-shelf" application. Since the innovation of induced pluripotent stem cells (iPSCs) by Yamanaka et al., extensive efforts have been made to prepare an unlimited cell source for regenerative medicine, that is, immunotherapy. In the autologous grafting approach, iPSCs prepare the desired cell source for generating autologous CAR-T cells through more accessible and available sources. In addition, generating iPSC-derived CAR-T cells is a promising approach to achieving a suitable source for producing an allogeneic CAR-T cell product. In brief, the first step is reprogramming somatic cells (accessible from peripheral blood, skin, etc.) to iPSCs. In the next step, CAR expression and T cell lineage differentiation should be applied in different arrangements. In addition, in an allogeneic manner, human leukocyte antigen/T cell receptor (TCR) deficiency should be applied in iPSC colonies. The allogeneic iPSC-derived CAR-T cell experiments showed that simultaneous performance of HLA/TCR deficiency, CAR expression, and T cell lineage differentiation could bring the production to the highest efficacy in generating allogeneic iPSC-derived CAR-T cells.

中文翻译：

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诱导多能干细胞衍生的嵌合抗原受体 T 细胞：干细胞与免疫疗法的交叉点。

嵌合抗原受体（CAR）T细胞疗法是一种有前景的细胞免疫疗法，适用于多种癌症。高生产成本、免疫排斥、细胞产品的异质性、有限的细胞来源、有限的扩展性以及相对较长的生产时间，导致需要实现一种通用的同种异体 CAR-T 细胞产品以供“现成”应用。自从Yamanaka等人创新诱导多能干细胞（iPSC）以来，人们为制备再生医学（即免疫疗法）的无限细胞来源做出了广泛的努力。在自体移植方法中，iPSC 通过更容易获得的来源来制备产生自体 CAR-T 细胞所需的细胞来源。此外，生成 iPSC 衍生的 CAR-T 细胞是获得生产同种异体 CAR-T 细胞产品的合适来源的一种有前景的方法。简而言之，第一步是将体细胞（可从外周血、皮肤等获取）重新编程为 iPSC。下一步，CAR表达和T细胞谱系分化应该以不同的方式应用。此外，应以同种异体的方式将人类白细胞抗原/T细胞受体（TCR）缺陷应用于iPSC集落中。同种异体 iPSC 衍生的 CAR-T 细胞实验表明，同时进行 HLA/TCR 缺陷、CAR 表达和 T 细胞谱系分化可以使生产同种异体 iPSC 衍生的 CAR-T 细胞达到最高功效。