Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Biomed Pharmacother. 2023 Sep;165:115123. doi: 10.1016/j.biopha.2023.115123. Epub 2023 Jul 4.
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.
嵌合抗原受体(CAR)修饰免疫细胞的过继细胞疗法(ACT)已经取得了很大进展,美国 FDA 已经批准了六种 CAR-T 细胞产品用于治疗血液系统恶性肿瘤。与 CAR-T 细胞相比,CAR-NK 细胞因其多种杀伤机制、更高的安全性和更广泛的来源而引起了越来越多的关注。诱导多能干细胞(iPSC)衍生的自然杀伤(iPSC-NK)细胞具有成熟的表型和强大的细胞溶解活性,并且能够提供同质的 CAR-NK 细胞群体,可扩增至临床规模。因此,iPSC 衍生的 CAR-NK(CAR-iNK)细胞可作为癌症免疫治疗的标准化和“即用型”产品。在这篇综述中,我们总结了 CAR-iNK 细胞的制造技术、遗传修饰策略、临床前和临床证据的现状,并讨论了 CAR-iNK 细胞治疗作为一种新型细胞免疫疗法在癌症中的挑战和未来前景。
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