Wang Y W, Tang Y M
Department/Center of Hematology-oncology, Children's Hospital of Zhejiang University School of Medicine; Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province; National Clinical Research Center for Child Health, Hangzhou 310003, China.
Zhonghua Xue Ye Xue Za Zhi. 2025 May 14;46(5):481-488. doi: 10.3760/cma.j.cn121090-20240911-00343.
Chimeric antigen receptor (CAR) T-cell therapy has achieved breakthroughs in treating relapsed/refractory B-cell malignancies. However, it still faces challenges, including complex manufacturing processes, limited indications, T-cell exhaustion, and insufficient durability of therapeutic efficacy. CRISPR/Cas9, a highly efficient and relatively simple gene-editing technology, offers new avenues for overcoming these limitations. This review briefly outlines the working mechanism of CRISPR/Cas9 and focuses on its recent applications and clinical practices in developing universal CAR T-cells, enhancing T-cell function, and extending CAR T-cell therapy to T-cell and myeloid leukemias. Furthermore, this review highlights optimization strategies developed over the past two years to enhance the editing precision, delivery efficiency, and safety of the CRISPR/Cas9 system, aiming to provide insights for the optimal design and clinical application of CAR T-cell therapy.
嵌合抗原受体（CAR）T细胞疗法在治疗复发/难治性B细胞恶性肿瘤方面取得了突破。然而，它仍然面临挑战，包括复杂的制造过程、有限的适应症、T细胞耗竭以及治疗效果的持久性不足。CRISPR/Cas9是一种高效且相对简单的基因编辑技术，为克服这些限制提供了新途径。本文简要概述了CRISPR/Cas9的工作机制，并重点介绍了其在开发通用CAR T细胞、增强T细胞功能以及将CAR T细胞疗法扩展至T细胞和髓系白血病方面的最新应用和临床实践。此外，本文还强调了过去两年中为提高CRISPR/Cas9系统的编辑精度、递送效率和安全性而开发的优化策略，旨在为CAR T细胞疗法的优化设计和临床应用提供见解。
