Chen Yi-Ju, Abila Bams, Mostafa Kamel Yasser
School of Cancer & Pharmaceutical Sciences, Faculty of Life & Sciences & Medicine, King's College, London SE1 9NH, UK.
Cancers (Basel). 2023 Jan 21;15(3):663. doi: 10.3390/cancers15030663.
The year 2017 was marked by the Food and Drug Administration (FDA) approval of the first two chimeric antigen receptor-T (CAR-T) therapies. The approved indications were for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and for the treatment of patients up to 25 years of age with acute lymphoblastic leukemia (ALL) that is refractory or in a second or later relapse. Since then, extensive research activities have been ongoing globally on different hematologic and solid tumors to assess the safety and efficacy of CAR-T therapy for these diseases. Limitations to CAR-T therapy became apparent from, e.g., the relapse in up to 60% of patients and certain side effects such as cytokine release syndrome (CRS). This led to extensive clinical activities aimed at overcoming these obstacles, so that the use of CAR-T therapy can be expanded. Attempts to improve on efficacy and safety include changing the CAR-T administration schedule, combining it with chemotherapy, and the development of next-generation CAR-T therapies, e.g., through the use of CAR-natural killer (CAR-NK) and CAR macrophages (CAR-Ms). This review will focus on new CAR-T treatment strategies in hematologic malignancies, clinical trials aimed at improving efficacy and addressing side effects, the challenges that CAR-T therapy faces in solid tumors, and the ongoing research aimed at overcoming these challenges.
2017年，美国食品药品监督管理局（FDA）批准了首批两种嵌合抗原受体T细胞（CAR-T）疗法，具有里程碑意义。获批的适应症为治疗复发或难治性弥漫性大B细胞淋巴瘤（DLBCL），以及治疗25岁及以下难治性或处于第二次及后续复发阶段的急性淋巴细胞白血病（ALL）患者。自那时起，全球范围内针对不同血液系统疾病和实体瘤展开了广泛的研究活动，以评估CAR-T疗法对这些疾病的安全性和有效性。CAR-T疗法的局限性逐渐显现，例如高达60%的患者会出现复发，以及某些副作用，如细胞因子释放综合征（CRS）。这促使人们开展了广泛的临床研究活动，旨在克服这些障碍，从而扩大CAR-T疗法的应用范围。在提高疗效和安全性方面所做的尝试包括改变CAR-T的给药方案、将其与化疗联合使用，以及开发下一代CAR-T疗法，例如通过使用CAR-自然杀伤细胞（CAR-NK）和CAR-巨噬细胞（CAR-M）。本综述将聚焦于血液系统恶性肿瘤的新型CAR-T治疗策略、旨在提高疗效和解决副作用的临床试验、CAR-T疗法在实体瘤中面临的挑战，以及为克服这些挑战而正在进行的研究。
