Abstract：
Adoptive cell therapies (ACT) based on chimeric antigen receptor (CAR)-modified immune cells have made great progress with six CAR-T cell products approved by the U.S. FDA for hematological malignancies. Compared with CAR-T cells, CAR-NK cells have attracted increasing attention owing to their multiple killing mechanisms, higher safety profile, and broad sources. Induced pluripotent stem cell (iPSC)-derived NK (iPSC-NK) cells possess a mature phenotype and potent cytolytic activity, and can provide a homogeneous population of CAR-NK cells that can be expanded to clinical scale. Thus, iPSC-derived CAR-NK (CAR-iNK) cells could be used as a standardized and \"off-the-shelf\" product for cancer immunotherapy. In this review, we summarize the current status of the manufacturing techniques, genetic modification strategies, preclinical and clinical evidence of CAR-iNK cells, and discuss the challenges and future prospects of CAR-iNK cell therapy as a novel cellular immunotherapy in cancer.
摘要：
基于嵌合抗原受体（CAR）修饰的免疫细胞的过继细胞疗法（ACT）已经取得了很大的进展，美国FDA批准了6种CAR-T细胞产品用于血液系统恶性肿瘤。与CAR-T细胞相比，CAR-NK细胞由于其多种杀伤机制而受到越来越多的关注,更高的安全性，和广泛的来源。诱导多能干细胞（iPSC）衍生的NK（iPSC-NK）细胞具有成熟的表型和有效的细胞溶解活性，并且可以提供可以扩展到临床规模的CAR-NK细胞的同质群体。因此，iPSC衍生的CAR-NK（CAR-iNK）细胞可用作癌症免疫治疗的标准化和“现成”产品。在这次审查中,我们总结了制造技术的现状，转基因策略，CAR-iNK细胞的临床前和临床证据，并讨论了CAR-iNK细胞疗法作为癌症新型细胞免疫疗法的挑战和未来前景。
