Almaeen Abdulrahman H, Abouelkheir Mohamed
Department of Pathology, Pathology Division, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia.
Department of Pharmacology and Therapeutics, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia.
Biomedicines. 2023 Oct 2;11(10):2693. doi: 10.3390/biomedicines11102693.
The currently available treatment for acute lymphoblastic leukemia (ALL) is mainly dependent on the combination of chemotherapy, steroids, and allogeneic stem cell transplantation. However, refractoriness and relapse (R/R) after initial complete remission may reach up to 20% in pediatrics. This percentage may even reach 60% in adults. To overcome R/R, a new therapeutic approach was developed using what is called chimeric antigen receptor-modified (CAR) T-cell therapy. The Food and Drug Administration (FDA) in the United States has so far approved four CAR T-cells for the treatment of ALL. Using this new therapeutic strategy has shown a remarkable success in treating R/R ALL. However, the use of CAR T-cells is expensive, has many imitations, and is associated with some adverse effects. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are two common examples of these adverse effects. Moreover, R/R to CAR T-cell therapy can take place during treatment. Continuous development of this therapeutic strategy is ongoing to overcome these limitations and adverse effects. The present article overviews the use of CAR T-cell in the treatment of ALL, summarizing the results of relevant clinical trials and discussing future prospects intended to improve the efficacy of this therapeutic strategy and overcome its limitations.
目前急性淋巴细胞白血病（ALL）的可用治疗方法主要依赖于化疗、类固醇和异基因干细胞移植的联合应用。然而，在儿科患者中，初始完全缓解后的难治性和复发（R/R）率可能高达20%。在成人中，这一比例甚至可能达到60%。为了克服R/R，人们开发了一种新的治疗方法，即使用所谓的嵌合抗原受体修饰（CAR）T细胞疗法。美国食品药品监督管理局（FDA）迄今为止已批准了四种CAR T细胞用于治疗ALL。使用这种新的治疗策略在治疗R/R ALL方面已取得显著成功。然而，CAR T细胞的使用成本高昂，存在诸多限制，并且伴有一些不良反应。细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）就是这些不良反应的两个常见例子。此外，在治疗过程中可能会出现对CAR T细胞疗法的R/R情况。目前正在持续研发这种治疗策略，以克服这些限制和不良反应。本文概述了CAR T细胞在ALL治疗中的应用，总结了相关临床试验的结果，并讨论了旨在提高这种治疗策略的疗效并克服其局限性的未来前景。
