Shenzhen Laboratory of Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
University of Chinese Academy of Sciences, Beijing, China.
Immunology. 2019 Oct;158(2):63-69. doi: 10.1111/imm.13094. Epub 2019 Aug 14.
Natural killer cells are potent cytotoxic lymphocytes specialized in recognizing and eliminating transformed cells, and in orchestrating adaptive anti-tumour immunity. However, NK cells are usually functionally exhausted in the tumour microenvironment. Strategies such as checkpoint blockades are under investigation to overcome NK cell exhaustion in order to boost anti-tumour immunity. The discovery and development of the CRISPR/Cas9 technology offer a flexible and efficient gene-editing capability in modulating various pathways that mediate NK cell exhaustion, and in arming NK cells with novel chimeric antigen receptors to specifically target tumour cells. Despite the high efficiency in its gene-editing capability, difficulty in the delivery of the CRISPR/Cas9 system remains a major bottleneck for its therapeutic applications, particularly for NK cells. The current review discusses feasible approaches to deliver the CRISPR/Cas9 systems, as well as potential strategies in gene-editing for NK cell immunotherapy for cancers.
自然杀伤细胞是一种具有强大细胞毒性的淋巴细胞,专门用于识别和消除转化细胞,并协调适应性抗肿瘤免疫。然而,NK 细胞在肿瘤微环境中通常功能耗竭。目前正在研究检查点阻断等策略,以克服 NK 细胞衰竭,从而增强抗肿瘤免疫。CRISPR/Cas9 技术的发现和发展提供了一种灵活高效的基因编辑能力,可以调节介导 NK 细胞衰竭的各种途径,并为 NK 细胞配备新型嵌合抗原受体,以特异性靶向肿瘤细胞。尽管其基因编辑能力效率很高,但 CRISPR/Cas9 系统的递送仍然是其治疗应用的主要瓶颈,特别是对于 NK 细胞。本综述讨论了递送 CRISPR/Cas9 系统的可行方法,以及用于癌症 NK 细胞免疫治疗的基因编辑的潜在策略。
Immunology. 2019-8-14
Stem Cells Transl Med. 2024-3-15
Methods Mol Biol. 2020
Recent Results Cancer Res. 2016
Front Immunol. 2025-4-7
J Gastroenterol. 2024-12
Front Med. 2024-10
Pharmaceutics. 2024-8-29
Clin Transl Oncol. 2024-7
Cell Death Dis. 2024-1-15
Cancer Immunol Immunother. 2018-12-6
Science. 2018-8-31
Nat Biotechnol. 2018-7-30
Proc Natl Acad Sci U S A. 2018-4-23