Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.
Department of Pathology, College of Medicine, Qassim University, Buraydah, Saudi Arabia.
Int J Nanomedicine. 2023 Sep 29;18:5531-5559. doi: 10.2147/IJN.S424872. eCollection 2023.
The recent developments in the study of clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) system have revolutionized the art of genome-editing and its applications for cellular differentiation and immune response behavior. This technology has further helped in understanding the mysteries of cancer progression and possible designing of novel antitumor immunotherapies. CRISPR/Cas9-based genome-editing is now often used to engineer universal T-cells, equipped with recombinant T-cell receptor (TCR) or chimeric antigen receptor (CAR). In addition, this technology is used in cytokine stimulation, antibody designing, natural killer (NK) cell transfer, and to overcome immune checkpoints. The innovative potential of CRISPR/Cas9 in preparing the building blocks of adoptive cell transfer (ACT) immunotherapy has opened a new window of antitumor immunotherapy and some of them have gained FDA approval. The manipulation of immunogenetic regulators has opened a new interface for designing, implementation and interpretation of CRISPR/Cas9-based screening in immuno-oncology. Several cancers like lymphoma, melanoma, lung, and liver malignancies have been treated with this strategy, once thought to be impossible. The safe and efficient delivery of CRISPR/Cas9 system within the immune cells for the genome-editing strategy is a challenging task which needs to be sorted out for efficient immunotherapy. Several targeting approaches like virus-mediated, electroporation, microinjection and nanoformulation-based methods have been used, but each procedure offers some limitations. Here, we elaborate the recent updates of cancer management through immunotherapy in partnership with CRISPR/Cas9 technology. Further, some innovative methods of targeting this genome-editing system within the immune system cells for reprogramming them, as a novel strategy of anticancer immunotherapy is elaborated. In addition, future prospects and clinical trials are also discussed.
近年来，对成簇规律间隔短回文重复序列/相关蛋白 9（CRISPR/Cas9）系统的研究进展彻底改变了基因组编辑技术，并将其应用于细胞分化和免疫反应行为。这项技术进一步帮助我们揭开了癌症进展的奥秘，并可能设计出新的抗肿瘤免疫疗法。基于 CRISPR/Cas9 的基因组编辑技术现在常用于构建通用 T 细胞，这些细胞配备了重组 T 细胞受体（TCR）或嵌合抗原受体（CAR）。此外，该技术还用于细胞因子刺激、抗体设计、自然杀伤（NK）细胞转移以及克服免疫检查点。CRISPR/Cas9 在制备过继细胞转移（ACT）免疫疗法的构建模块方面的创新潜力为抗肿瘤免疫疗法开辟了新的窗口，其中一些已获得 FDA 批准。免疫遗传调控因子的操纵为基于 CRISPR/Cas9 的筛选在免疫肿瘤学中的设计、实施和解释开辟了新的界面。几种癌症，如淋巴瘤、黑色素瘤、肺癌和肝癌，已经使用这种策略进行了治疗，这种策略曾经被认为是不可能的。在免疫细胞内安全有效地递送到 CRISPR/Cas9 系统以实现基因组编辑策略是一项具有挑战性的任务，需要加以解决以实现有效的免疫疗法。已经使用了几种靶向方法，如病毒介导、电穿孔、微注射和基于纳米制剂的方法，但每种方法都存在一些局限性。在这里，我们详细阐述了免疫疗法与 CRISPR/Cas9 技术合作治疗癌症的最新进展。此外，还详细阐述了一些创新的靶向方法，用于在免疫细胞内靶向该基因组编辑系统，作为一种新型的抗癌免疫疗法策略。此外，还讨论了未来的前景和临床试验。
