National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
Int J Mol Sci. 2023 Aug 1;24(15):12317. doi: 10.3390/ijms241512317.
As an emerging treatment strategy for malignant tumors, chimeric antigen receptor T (CAR-T) cell therapy has been widely used in clinical practice, and its efficacy has been markedly improved in the past decade. However, the clinical effect of CAR-T therapy is not so satisfying, especially in solid tumors. Even in hematologic malignancies, a proportion of patients eventually relapse after receiving CAR-T cell infusions, owing to the poor expansion and persistence of CAR-T cells. Recently, CRISPR/Cas9 technology has provided an effective approach to promoting the proliferation and persistence of CAR-T cells in the body. This technology has been utilized in CAR-T cells to generate a memory phenotype, reduce exhaustion, and screen new targets to improve the anti-tumor potential. In this review, we aim to describe the major causes limiting the persistence of CAR-T cells in patients and discuss the application of CRISPR/Cas9 in promoting CAR-T cell persistence and its anti-tumor function. Finally, we investigate clinical trials for CRISPR/Cas9-engineered CAR-T cells for the treatment of cancer.
嵌合抗原受体 T（CAR-T）细胞疗法作为一种恶性肿瘤的新兴治疗策略，已广泛应用于临床实践，其疗效在过去十年中得到显著提高。然而，CAR-T 疗法的临床效果并不那么令人满意，特别是在实体瘤中。即使在血液恶性肿瘤中，一部分患者在接受 CAR-T 细胞输注后最终还是会复发，这是由于 CAR-T 细胞在体内的扩增和持续存在情况不佳。最近，CRISPR/Cas9 技术为促进 CAR-T 细胞在体内的增殖和持续存在提供了一种有效的方法。该技术已被应用于 CAR-T 细胞中，以产生记忆表型、减少衰竭，并筛选新的靶点来提高抗肿瘤潜能。在本综述中，我们旨在描述限制 CAR-T 细胞在患者体内持续存在的主要原因，并讨论 CRISPR/Cas9 在促进 CAR-T 细胞持续存在及其抗肿瘤功能方面的应用。最后，我们研究了 CRISPR/Cas9 工程 CAR-T 细胞治疗癌症的临床试验。
