提前为CD19 CAR-T细胞治疗铺平道路

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Paving the road ahead for CD19 CAR T-cell therapy.

PURPOSE OF REVIEW:

Modern immunotherapies, most notably in the form of anti-CD19 chimeric antigen receptor (CAR) T cells, have produced significant clinical responses in otherwise refractory pre-B-cell acute lymphoblastic leukemia patients. Several groups have simultaneously reported robust response rates in children and **s alike. These early studies indicate an impending shift in paradigm for the treatment of acute lymphoblastic leukemia. Incorporating CD19 CAR T-cell therapy into upfront or salvage regimens has its challenges and opportunities.

RECENT FINDINGS:

Most CD19 CAR T-cell products in trial today are excellent at inducing minimal residual disease negative remissions, and most responding patients experience cytokine release syndrome and/or neurotoxicity. The challenges facing the CAR community involve how best to minimize the severity of cytokine release syndrome and neurotoxicity while maximizing antitumor efficacy, determining what role this therapy will play for the prophylaxis and treatment of central nervous system leukemia, and its implications on subsequent hematopoietic stem cell transplant given the emergence of CD19-negative relapses.

SUMMARY:

CD19 CAR T-cell therapy is a powerful new tool in the oncologist's arsenal. How it is incorporated into standard practice and how it will shift survival curves are the exciting questions that are waiting to be answered.

提前为CD19 CAR-T细胞治疗铺平道路

综述的目的：

现代免疫治疗，大多是以靶向CD19嵌合抗原受体修饰的T细胞疗法，在复发性B细胞急性淋巴细胞白血病患者的治疗中展现了明显的治疗效果。有一些团队同时报道了在成人和儿童患者中表现出良好的有效性。这些早期研究显示了对于急性淋巴细胞白血病的治疗模式即将发生改变。当然，结合CD19 CAR-T细胞疗法作为前期或者抢救方案还将面临一些挑战和机遇。

最新的发现

试验中的大多数CD19CAR-T细胞产品擅长诱导微小残留病的负缓解，大多数患者会经历细胞因子释放综合征和/或神经毒性。CAR-T细胞治疗面临的挑战是如何最大限度地减少抗肿瘤疗效的细胞因子释放综合征和神经毒性的严重程度，确定这种疗**对中枢神经系统白血病的预防和治疗起到什么样的作用，以及其对后续的造血干细胞移植出现的CD19阴性复发的作用。

总结：

CD19 CAR-T细胞治疗是肿瘤科医生一个强有力的工具。如何将其纳入标准治疗规范，如何转变患者的生存曲线是接下来需要解决的最重要的问题。       

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