ABSTRACT

Introduction

Though 85% of children and young adults with acute lymphoblastic leukemia (ALL) are cured, until recently, the prognosis of relapsed or refractory disease has been dismal. The advent of chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of relapsed/refractory ALL. The most well-studied, successful CARs are autologous, murine-based anti-CD19 CARs, but new constructs are currently under clinical investigation.

Areas covered

This review describes the history and design of CAR T cells, clinical trial outcomes of anti-CD19 and newer CARs, treatment-related toxicities including cytokine release syndrome and neurotoxicity, and issues with resistance and relapse. A search of PubMed and clinicaltrials.gov spanning from 2012-present was used to select original reports investigating the use of CAR T in pediatric patients.

Expert opinion

CD19-targeted CARs have demonstrated remarkable response rates and produced durable remissions in very high-risk pediatric patient populations. The therapies, however, are limited by unique treatment-related toxicities and considerable rates of antigen-positive and antigen-negative relapses. Current research efforts focused on elucidating mechanisms of resistance/relapse and on developing strategies to prevent and treat relapse are critical to optimizing the use of CAR-T. In addition, ongoing trials testing CARs earlier in therapy and for new indications are key to informing their widespread usage.

中文翻译：

---

嵌合抗原受体 T 细胞疗法治疗儿童和年轻成人 B 细胞急性淋巴细胞白血病。

 抽象的

 介绍

尽管 85% 的急性淋巴细胞白血病 (ALL) 儿童和年轻人可以治愈，但直到最近，复发或难治性疾病的预后一直很差。嵌合抗原受体 (CAR) T 细胞疗法的出现改变了复发/难治性 ALL 的治疗方法。研究最充分、最成功的 CAR 是自体、基于小鼠的抗 CD19 CAR，但新的构建体目前正在临床研究中。

 涵盖领域

这篇综述描述了 CAR T 细胞的历史和设计、抗 CD19 和新型 CAR 的临床试验结果、治疗相关的毒性（包括细胞因子释放综合征和神经毒性）以及耐药和复发问题。通过对 2012 年至今的 PubMed 和 ClinicalTrials.gov 的搜索，选择了调查 CAR T 在儿科患者中使用的原始报告。

 专家意见

针对 CD19 的 CAR 已表现出显着的缓解率，并在极高危儿科患者群体中产生了持久的缓解。然而，这些疗法受到独特的治疗相关毒性以及相当大的抗原阳性和抗原阴性复发率的限制。目前的研究工作重点是阐明耐药/复发机制以及制定预防和治疗复发的策略，这对于优化 CAR-T 的使用至关重要。此外，正在进行的治疗早期测试 CAR 和新适应症的试验是了解其广泛使用的关键。