Champalimaud Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal.
NOVA Medical School of NOVA University of Lisbon, Lisbon, Portugal.
Stem Cells Transl Med. 2024 Mar 15;13(3):230-242. doi: 10.1093/stcltm/szad087.
Natural killer (NK) cells are a subset of cytotoxic lymphocytes within the innate immune system. While they are naturally cytotoxic, genetic modifications can enhance their tumor-targeting capability, cytotoxicity, persistence, tumor infiltration, and prevent exhaustion. These improvements hold the potential to make NK-cell-based immunotherapies more effective in clinical applications. Currently, several viral and non-viral technologies are used to genetically modify NK cells. For nucleic acid delivery, non-viral methods such as electroporation, lipid nanoparticles, lipofection, and DNA transposons have gained popularity in recent years. On the other hand, viral methods including lentivirus, gamma retrovirus, and adeno-associated virus, remain widely used for gene delivery. Furthermore, gene editing techniques such as clustered regularly interspaced short-palindromic repeats-based, zinc finger nucleases, and transcription activator-like effector nucleases are the pivotal methodologies in this field. This review aims to provide a comprehensive overview of chimeric antigen receptor (CAR) arming strategies and discuss key gene editing techniques. These approaches collectively aim to enhance NK cell/NK cell CAR-based immunotherapies for clinical translation.
自然杀伤 (NK) 细胞是先天免疫系统中细胞毒性淋巴细胞的一个子集。虽然它们天生具有细胞毒性,但遗传修饰可以增强其肿瘤靶向能力、细胞毒性、持久性、肿瘤浸润能力,并防止衰竭。这些改进有可能使基于 NK 细胞的免疫疗法在临床应用中更有效。目前,有几种病毒和非病毒技术可用于遗传修饰 NK 细胞。对于核酸传递,近年来非病毒方法,如电穿孔、脂质纳米粒、脂质体转染和 DNA 转座子,已变得流行。另一方面,包括慢病毒、γ逆转录病毒和腺相关病毒在内的病毒方法仍然广泛用于基因传递。此外,基因编辑技术,如基于簇状规则间隔短回文重复序列的、锌指核酸酶和转录激活因子样效应物核酸酶,是该领域的关键方法学。本综述旨在提供嵌合抗原受体 (CAR) 武装策略的全面概述,并讨论关键的基因编辑技术。这些方法共同旨在增强 NK 细胞/NK 细胞 CAR 为基础的免疫疗法的临床转化。
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