决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.
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。
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。
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.
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