CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:IPSC-derived CAR-NK cells for cancer immunotherapy.
IPSC-derived CAR-NK cells for cancer immunotherapy.
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基于嵌合抗原受体(CAR)修饰免疫细胞的过继细胞治疗(ACT)取得显著进展,美国FDA已批准6种用于血液系统恶性肿瘤的CAR-T 细胞产品。与CAR-T 细胞相比,CAR-NK细胞具有多种杀伤机制、安全性较高且来源广泛,因此受到越来越多关注。诱导多能干细胞(iPSC)来源的NK(iPSC-NK)细胞具有成熟表型和强细胞毒活性,并可提供均一、可扩增至临床规模的CAR-NK细胞群。因此,iPSC来源的CAR-NK(CAR-iNK)细胞有望成为标准化的“现货型”癌症免疫治疗产品。本综述总结CAR-iNK细胞制造技术、基因修饰策略及临床前和临床证据,并讨论CAR-iNK细胞治疗作为新型细胞免疫疗法面临的挑战和未来前景。
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.
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