Fry Terry J, Mackall Crystal L
1Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Hematology Am Soc Hematol Educ Program. 2013;2013:348-53. doi: 10.1182/asheducation-2013.1.348.
Substantial progress has been made in the treatment of precursor B-cell acute lymphoblastic leukemia (B-ALL), but recurrent disease remains a leading cause of death in children due to cancer and outcomes for adults with B-ALL remain poor. Recently, complete clinical responses have been observed in small numbers of patients with B-ALL treated with adoptive immunotherapy using T cells genetically engineered to express chimeric antigen receptors (CARs) targeting CD19, a cell surface molecule present in essentially all cases of B-ALL. Preclinical data suggest that CARs targeting CD22, another antigen present in the majority of B-ALL cases, are similarly potent. Several clinical studies already under way will soon more clearly define the rate of response to this novel therapy in B-ALL. Further work is needed to identify optimal platforms for CAR-based adoptive immunotherapy for leukemia, to establish guidelines for managing toxicity, and to determine whether the remissions induced by this approach can be rendered durable.
前体B细胞急性淋巴细胞白血病(B-ALL)的治疗已取得重大进展,但复发疾病仍是儿童癌症死亡的主要原因,且成人B-ALL的治疗效果仍然较差。最近,在少数接受过继性免疫疗法治疗的B-ALL患者中观察到了完全临床缓解,该疗法使用经过基因工程改造的T细胞来表达靶向CD19的嵌合抗原受体(CAR),CD19是一种几乎在所有B-ALL病例中都存在的细胞表面分子。临床前数据表明,靶向CD22(另一种在大多数B-ALL病例中存在的抗原)的CAR同样有效。目前正在进行的几项临床研究将很快更清楚地确定这种新型疗法在B-ALL中的反应率。需要进一步开展工作,以确定基于CAR的白血病过继性免疫疗法的最佳平台,制定毒性管理指南,并确定这种方法诱导的缓解是否可以持久。