Division of Hematology Oncology, University of Pennsylvania, 3400 Civic Center Boulevard, PCAM 2 West Pavilion, Philadelphia, Pennsylvania, 19104.
Am J Hematol. 2016 Jan;91(1):146-50. doi: 10.1002/ajh.24238.
Chimeric antigen receptors (CARs) can be introduced into T-cells redirecting them to target specific tumor antigens. CAR-modified T cells targeting CD19 have shown remarkable activity against CD19+ malignancies including B cell acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphomas (NHL). Complete remission rates as high as 90% have been observed for patients with relapsed and refractory ALL and greater than 50% response rates have been seen in heavily pre-treated CLL and NHL. Excitingly, some remissions have been durable without any additional therapy, a finding which correlates with in-vivo T-cell persistence and B-cell aplasia. The major treatment related toxicities include B-cell aplasia, neurologic toxicities, and a potentially severe cytokine release syndrome. This review summarizes outcomes for patients treated with CD19-CAR T-cells while exploring the field's challenges and future directions.
嵌合抗原受体 (CAR) 可被引入 T 细胞,从而将其重定向至靶向特定肿瘤抗原。针对 CD19 的 CAR 修饰 T 细胞对包括 B 细胞急性淋巴细胞白血病 (ALL)、慢性淋巴细胞白血病 (CLL) 和非霍奇金淋巴瘤 (NHL) 在内的 CD19+恶性肿瘤显示出显著的活性。对于复发和难治性 ALL 患者,观察到高达 90%的完全缓解率,在经过大量预处理的 CLL 和 NHL 中,观察到超过 50%的缓解率。令人兴奋的是,一些缓解是持久的,无需任何额外的治疗,这与体内 T 细胞的持久性和 B 细胞发育不良有关。主要的治疗相关毒性包括 B 细胞发育不良、神经毒性和潜在的严重细胞因子释放综合征。本综述总结了接受 CD19-CAR T 细胞治疗的患者的结果,同时探讨了该领域的挑战和未来方向。