肿瘤细胞治疗研究
英文原题：Targeting GD2 with CAR-T Cell Therapy in Neuroblastoma: Updates, Challenges, and Future Perspectives.
在靶向 GD2 的 CAR-T 细胞治疗复发/难治性神经母细胞瘤的早期试验中，未观察到剂量限制性毒性。
综述目的：高危神经母细胞瘤仍是具有挑战性的儿童癌症；尽管多模式治疗不断进步，患者生存率仍不理想。本综述旨在批判性总结 GD2 靶向嵌合抗原受体（CAR）T 细胞疗法治疗神经母细胞瘤的近期进展，并强调其改善长期结局的潜力。 近期发现：GD2 靶向 CAR-T 治疗复发或难治性神经母细胞瘤的早期临床试验中，未观察到剂量限制性毒性。客观缓解率为 6%–33%，有患者获得持久完全缓解且缓解持续超过 10 年。疾病稳定率最高达 55%。细胞因子释放综合征报告发生率为 0–90%，通常为轻度；神经毒性罕见。多项研究证实 CAR-T 细胞能够扩增并迁移至肿瘤部位，但在实体瘤情境下，这些过程存在差异且常受限。GD2 靶向 CAR-T 显示有限但可测量的临床活性，尤其在微小残留病情境中，整体安全性可接受。持续创新 CAR 设计并将其纳入多模式治疗策略，有望改善这一侵袭性儿童癌症的长期结局。
PURPOSE OF REVIEW: High-risk neuroblastoma remains a challenging pediatric cancer, with survival rates lagging despite advances in multimodal therapy. This review aims to critically synthesize recent advances in GD2-directed chimeric antigen receptor (CAR) T cell therapy for neuroblastoma and to highlight its potential to improve long-term outcomes. RECENT FINDINGS: In early-phase trials of GD2-directed CAR-T cell therapy for relapsed or refractory neuroblastoma, no dose-limiting toxicities were observed. Objective responses ranged from 6% to 33%, with durable complete remissions reported beyond 10 years. Stable disease occurred in up to 55% of patients. Cytokine release syndrome was reported in 0-90% of cases, generally mild, and neurotoxicity was rare. CAR-T cell expansion and trafficking to tumor sites have been demonstrated in several studies, although they remain variable and often limited in solid tumor settings. GD2-directed CAR-T cell therapy demonstrates limited but measurable clinical activity, particularly in minimal residual disease settings, with an overall acceptable safety profile. Continued innovation in CAR design and integration into multimodal strategies may improve long-term outcomes for this aggressive pediatric cancer.
MEMBER ACCOUNT
登录成功会直接打开下一页。
