Luskin Marlise R, DeAngelo Daniel J
Harvard Medical School, Boston, MA, USA.
Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.
Curr Hematol Malig Rep. 2017 Aug;12(4):370-379. doi: 10.1007/s11899-017-0394-x.
Over half of patients diagnosed with B-cell acute lymphoblastic leukemia (ALL) develop relapsed or refractory disease. Traditional chemotherapy salvage is inadequate, and new therapies are needed. Chimeric antigen receptor (CAR) T cell therapy is a novel, immunologic approach where T cells are genetically engineered to express a CAR conferring specificity against a target cell surface antigen, most commonly the pan-B-cell marker CD19. After infusion, CAR T cells expand and persist, allowing ongoing tumor surveillance. Several anti-CD19 CAR T cell constructs have induced high response rates in heavily pre-treated populations, although durability of response varied. Severe toxicity (cytokine release syndrome and neurotoxicity) is the primary constraint to broad implementation of CAR T cell therapy. Here, we review the experience of CAR T cell therapy for ALL and ongoing efforts to modify existing technology to improve efficacy and decrease toxicity. As an anti-CD19 CAR T cell construct may be FDA approved soon, we focus on issues relevant to practicing clinicians.
超过半数被诊断为B细胞急性淋巴细胞白血病(ALL)的患者会出现复发或难治性疾病。传统的化疗挽救方案并不充分,因此需要新的治疗方法。嵌合抗原受体(CAR)T细胞疗法是一种新型的免疫疗法,通过基因工程改造T细胞,使其表达一种针对靶细胞表面抗原(最常见的是泛B细胞标志物CD19)的CAR。输注后,CAR T细胞会扩增并持续存在,从而实现持续的肿瘤监测。尽管反应的持久性各不相同,但几种抗CD19 CAR T细胞构建体已在经过大量预处理的人群中诱导出了高反应率。严重毒性(细胞因子释放综合征和神经毒性)是CAR T细胞疗法广泛应用的主要限制因素。在此,我们回顾了CAR T细胞疗法治疗ALL的经验,以及为改进现有技术以提高疗效和降低毒性而正在进行的努力。由于一种抗CD19 CAR T细胞构建体可能很快会获得美国食品药品监督管理局(FDA)的批准,我们重点关注与临床医生实践相关的问题。
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