Leukemia ( IF 12.8 ) Pub Date : 2024-10-25 , DOI: 10.1038/s41375-024-02444-y Tao Lei, Yazhuo Wang, Yuchen Zhang, Yufei Yang, Jiaying Cao, Jiansong Huang, Jiali Chen, Huajing Chen, Jiayi Zhang, Luzheng Wang, Xinjie Xu, Robert Peter Gale, Liang Wang
Chimeric Antigen Receptor (CAR)-T-cell therapy has revolutionized cancer immune therapy. However, challenges remain including increasing efficacy, reducing adverse events and increasing accessibility. Use of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology can effectively perform various functions such as precise integration, multi-gene editing, and genome-wide functional regulation. Additionally, CRISPR screening using large-scale guide RNA (gRNA) genetic perturbation provides an unbiased approach to understanding mechanisms underlying anti-cancer efficacy of CAR T-cells. Several emerging CRISPR tools with high specificity, controllability and efficiency are useful to modify CAR T-cells and identify new targets. In this review we summarize potential uses of the CRISPR system to improve results of CAR T-cells therapy including optimizing efficacy and safety and, developing universal CAR T-cells. We discuss challenges facing CRISPR gene editing and propose solutions highlighting future research directions in CAR T-cell therapy.
中文翻译:
利用 CRISPR 基因编辑技术优化 CAR T 细胞疗法的疗效、安全性和可及性
嵌合抗原受体 (CAR)-T 细胞疗法彻底改变了癌症免疫疗法。然而,挑战仍然存在,包括提高疗效、减少不良事件和增加可及性。使用成簇规则间隔短回文重复序列 (CRISPR) 技术可以有效地执行各种功能,例如精确整合、多基因编辑和全基因组功能调控。此外,使用大规模向导 RNA (gRNA) 遗传扰动的 CRISPR 筛选为了解 CAR T 细胞抗癌功效的潜在机制提供了一种无偏倚的方法。几种具有高特异性、可控性和效率的新兴 CRISPR 工具可用于修饰 CAR T 细胞和识别新靶点。在这篇综述中,我们总结了 CRISPR 系统在改善 CAR T 细胞治疗结果方面的潜在用途,包括优化疗效和安全性以及开发通用 CAR T 细胞。我们讨论了 CRISPR 基因编辑面临的挑战,并提出了突出 CAR T 细胞疗法未来研究方向的解决方案。