摘要
嵌合抗原受体T(chimeric antigen receptor T,CAR-T)细胞是通过基因工程技术将T细胞改造成针对肿瘤特异性抗原的新型杀伤细胞,具有特异性强、效率高、非MHC限制等优点,在复发/难治性血液系统肿瘤和部分实体瘤中取得良好的治疗效果。但目前CAR-T细胞治疗仍面临着缺乏"现货供应"的通用型CAR-T细胞、抑制性免疫微环境和T细胞耗竭等问题。近年来,锌指核酸酶(zinc finger nucleases,ZFNs)、转录激活子样效应因子核酸酶(transcription activator like effector nucleases,TALENs)、规律性重复短回文序列簇[clustered regularly interspaced short palindromic repeats/CRISPR-associated(Cas9),CRISPR/Cas9]等新型基因编辑技术被广泛应用于细胞免疫治疗,为解决上述问题带来了希望。本文综述了目前CAR-T细胞治疗的研究进展及存在问题,并探讨了3种主要的基因编辑技术改良CAR-T细胞治疗的策略,为CAR-T细胞的基础研究和临床治疗提供参考。
引文
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