肿瘤细胞治疗研究
英文原题：Adoptive T-Cell Therapy in Sarcomas.
越来越多的临床试验正在探索过继性 T 细胞疗法在肉瘤中的应用，其中多数通过工程化 T 细胞受体（TCR-T）靶向 NY-ESO-1 和 MAGE-A4。
综述目的：总结并评估肉瘤领域最新的过继 T 细胞疗法，重点关注治疗靶点、疗效、安全性及局限。最新进展：越来越多临床试验正在研究肉瘤过继 T 细胞疗法，多数采用工程化 T 细胞受体（TCR-T）靶向 NY-ESO-1 和 MAGE-A4。afamitresgene autoleucel 获 FDA 批准用于晚期滑膜肉瘤，letetresgene autoleucel 获得黏液样/圆细胞脂肪肉瘤突破性疗法认定，标志着重要转折。CAR-T 策略主要靶向 B7H3、GD2、FGFR4 和 HER2，创新方向包括双抗原靶向和安全开关。TIL（肿瘤浸润淋巴细胞）疗法（包括 lifileucel）正在与检查点抑制剂或溶瘤药物联合研究，以增强疗效并管理毒性。过继 T 细胞疗法在肉瘤中显示早期前景，尤其是 TCR-T。其挑战包括 HLA 限制、肿瘤异质性和制备复杂。未来可采用新型抗原、多靶点策略和联合方案，扩大患者适用范围并改善治疗结局。
PURPOSE OF REVIEW: To summarise and evaluate the latest adoptive T-cell therapies in sarcomas, focusing on therapeutic targets, efficacy, safety, and limitations. RECENT FINDINGS: An increasing number of clinical trials are investigating adoptive T-cell therapies in sarcomas, most targeting NY-ESO-1 and MAGE-A4 through engineered T-cell receptors (TCR-T). The FDA approval of afamitresgene autoleucel for advanced synovial sarcoma and the breakthrough designation of letetresgene autoleucel for myxoid/round cell liposarcoma signify a major turning point. Chimeric antigen receptor T strategies target mainly B7H3, GD2, FGFR4, and HER2, with innovations including dual antigen targeting and safety switches. Tumour infiltrating lymphocyte therapy, including lifileucel, is under investigation with checkpoint inhibitors or oncolytic agents to enhance efficacy and manage toxicity. Adoptive T-cell therapy demonstrates early promise in sarcomas, particularly TCR-T therapy. Challenges include HLA restriction, tumour heterogeneity, and manufacturing complexity. Future strategies involving novel antigens, multi-targeting, and combinatorial regimens could broaden patient eligibility and improve therapeutic outcomes.
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