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儿童实体瘤的嵌合抗原受体(CAR)-T 细胞疗法:当前突破、困境与策略

英文原题:Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.

PubMed 2026/09/05(内容时间) Exp Hematol Oncol Q1 · IF 17.5(JCR 2025)

研究概要

嵌合抗原受体(CAR)-T细胞疗法在儿童血液系统恶性肿瘤中已显示出显著的临床疗效;然而,其在儿童实体瘤中的应用仍处于研究阶段,并受到重大生物学和临床挑战的制约。

中文摘要

嵌合抗原受体(CAR)-T细胞疗法在儿童血液系统恶性肿瘤中已显示出显著的临床疗效;然而,其在儿童实体瘤中的应用仍处于研究阶段,并受到重大生物学和临床挑战的限制。关键障碍包括肿瘤异质性、抗原逃逸、T细胞耗竭、物理屏障和免疫抑制性肿瘤微环境、治疗相关毒性,以及儿科特有的考量因素,包括最佳给药剂量和潜在的长期发育后遗症。正在进行的研究集中于识别新的靶抗原、优化CAR结构、对CAR-T细胞进行基因工程改造,以及改进递送策略以应对这些障碍。在这篇综述中,我们总结了CAR-T细胞疗法在儿童实体瘤中的最新进展、持续存在的挑战和新兴策略。我们还讨论了CAR-T细胞疗法与化疗、放疗和免疫检查点抑制剂联合应用的合理组合策略,旨在提高治疗疗效和安全性。随着该领域的不断发展,CAR-T细胞疗法的进步可能会扩大儿童实体瘤的治疗选择,尽管仍需进一步的临床研究来确定其长期疗效和安全性。

展开英文摘要原文

Chimeric antigen receptor (CAR)-T cell therapy has demonstrated substantial clinical efficacy in pediatric hematologic malignancies; however, its application in pediatric solid tumors remains investigational and is constrained by substantial biological and clinical challenges. Key barriers comprise tumor heterogeneity, antigen escape, T-cell exhaustion, physical barriers and immunosuppressive tumor microenvironment, treatment-related toxicities, and pediatric-specific considerations, including optimal dosing and potential long-term developmental sequelae. Ongoing research focuses on identifying novel target antigens, optimizing CAR architectures, genetically engineering CAR-T cells, and improving delivery strategies to address these barriers. In this review, we summarize recent advances, persistent challenges, and emerging strategies for CAR-T cell therapy in pediatric solid tumors. We also discuss rational combination strategies involving CAR-T cell therapy with chemotherapy, radiotherapy, and immune checkpoint inhibitors aimed at improving therapeutic efficacy and safety. As the field continues to evolve, advances in CAR-T cell therapy may expand therapeutic options for pediatric solid tumors, although further clinical investigation is required to establish its long-term efficacy and safety.

论文信息

作者
Mai Y、Wang Z、Wang J、Song M、Xiang T、He Y、Chang AH、Zhang Y
第一作者单位
Department of Pediatric Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.China
通讯作者单位
Department of Pediatric Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China. zhangyzh@sysucc.org.cn.China
文献类型
综述
期刊
Experimental hematology & oncology2026 Sep 5
原文标识
PubMed 42701195 · DOI 10.1186/s40164-026-00822-z