Department of Clinical Laboratory Science, Young Researchers and Elites Club, Gorgan Branch, Islamic Azad University, Gorgan, Iran.
Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.
Biotechnol Bioeng. 2021 Oct;118(10):3691-3705. doi: 10.1002/bit.27882. Epub 2021 Jul 21.
Adoptive cell immunotherapy with chimeric antigen receptor T (CAR-T) cell has brought a revolutionary means of treatment for aggressive diseases such as hematologic malignancies and solid tumors. Over the last decade, the United States Food and Drug Administration (FDA) approved five types of CAR-T cell therapies for hematologic malignancies, including Idecabtagene vicleucel (Abecma), Lisocabtagene maraleucel (Breyanzi), Brexucabtagene autoleucel (Tecartus), Tisagenlecleucel (Kymriah), and Axicabtagene ciloleucel (Yescarta). Despite outstanding results gained from different clinical trials, CAR-T cell therapy is not free from side effects and toxicities, and needs careful investigations and improvements. Gene-editing technology, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, has emerged as a promising tool to address some of the CAR-T therapy hurdles. Using CRISPR/Cas9 technology, CAR expression as well as other cellular pathways can be modified in various ways to enhance CAR-T cells antitumor function and persistence in immunosuppressive tumor microenvironment. CRISPR/Cas9 technology can also be used to decrease CAR-T cell toxicities and side effects. Hereby, we discussed the practical challenges and hurdles related to the accuracy, efficiency, efficacy, safety, and delivery of CRISPR/Cas9 technology to the genetically engineered-T cells. Combining of these two state-of-the-art technologies, CRISPR/Cas9 and CAR-T cells, the field of oncology has an extraordinary opportunity to enter a new era of immunotherapy, which offers novel therapeutic options for different types of tumors.
嵌合抗原受体 T (CAR-T) 细胞的过继细胞免疫疗法为血液恶性肿瘤和实体瘤等侵袭性疾病带来了革命性的治疗手段。在过去的十年中，美国食品和药物管理局 (FDA) 批准了五种用于血液恶性肿瘤的 CAR-T 细胞疗法，包括 Idecabtagene vicleucel (Abecma)、Lisocabtagene maraleucel (Breyanzi)、Brexucabtagene autoleucel (Tecartus)、Tisagenlecleucel (Kymriah) 和 Axicabtagene ciloleucel (Yescarta)。尽管不同临床试验取得了显著成果，但 CAR-T 细胞疗法并非没有副作用和毒性，需要进行仔细的研究和改进。基因编辑技术、成簇规律间隔短回文重复 (CRISPR)/CRISPR 相关蛋白 9 (Cas9) 系统已成为解决一些 CAR-T 治疗障碍的有前途的工具。利用 CRISPR/Cas9 技术，可以以多种方式修饰 CAR 的表达和其他细胞途径，以增强 CAR-T 细胞在免疫抑制性肿瘤微环境中的抗肿瘤功能和持久性。CRISPR/Cas9 技术还可用于降低 CAR-T 细胞的毒性和副作用。在此，我们讨论了与 CRISPR/Cas9 技术的准确性、效率、疗效、安全性和向基因工程 T 细胞传递相关的实际挑战和障碍。将这两种最先进的技术——CRISPR/Cas9 和 CAR-T 细胞结合起来，肿瘤学领域有机会进入免疫治疗的新时代，为不同类型的肿瘤提供新的治疗选择。
