肿瘤细胞治疗研究
英文原题：TCR-engineered T cell therapy in solid tumors: State of the art and perspectives.
T 细胞工程改变了肿瘤免疫治疗的面貌。
T细胞工程改变了癌症免疫治疗格局。CAR-T 细胞治疗血液系统B细胞恶性肿瘤已显示显著疗效，但迄今其对实体瘤的临床影响较小。表达工程化T细胞受体的T细胞（TCR-T细胞）是一种有前景的治疗替代方案。其靶点范围不限于膜蛋白，而TCR固有特征（如抗原敏感性高、信号传导接近生理状态）可能改善肿瘤细胞识别和杀伤，同时提高T细胞持久性。本综述介绍靶向不同肿瘤抗原家族的TCR-T细胞临床结果，详细说明鉴定和优化TCR候选物的不同方法，并讨论TCR-T细胞疗法的挑战，包括毒性评估和耐药机制。最后，本文分享该领域的一些见解并指出未来方向。
T cell engineering has changed the landscape of cancer immunotherapy. Chimeric antigen receptor T cells have demonstrated a remarkable efficacy in the treatment of B cell malignancies in hematology. However, their clinical impact on solid tumors has been modest so far. T cells expressing an engineered T cell receptor (TCR-T cells) represent a promising therapeutic alternative. The target repertoire is not limited to membrane proteins, and intrinsic features of TCRs such as high antigen sensitivity and near-to-physiological signaling may improve tumor cell detection and killing while improving T cell persistence. In this review, we present the clinical results obtained with TCR-T cells targeting different tumor antigen families. We detail the different methods that have been developed to identify and optimize a TCR candidate. We also discuss the challenges of TCR-T cell therapies, including toxicity assessment and resistance mechanisms. Last, we share some perspectives and highlight future directions in the field.
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