重编程工程化自体 T 细胞以克服 Merkel 细胞癌患者的耐药性
Reprogramming engineered autologous T cells to overcome resistance in patients with Merkel cell carcinoma.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects.
Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects.
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为使T细胞重新靶向肿瘤细胞,可在体外工程化改造T细胞,使其表达癌抗原特异性T细胞受体(TCR),生成TCR工程化T细胞(TCR T)。与嵌合抗原受体(CAR)不同,TCR可识别由人类白细胞抗原(HLA)呈递、来源于细胞各区室蛋白的肽段。随着过继细胞疗法(ACT)治疗实体瘤的研究不断加强,TCR T细胞ACT受到越来越多关注。本文介绍CAR和TCR介导的T细胞抗原识别及信号转导机制差异,概述当前TCR T疗法识别的癌症抗原类别,并讨论抗原特异性TCR的发现、增强和验证方面的经典及新兴临床前策略。最后,本文综述TCR T疗法的当前临床试验格局,并讨论现有结果对未来工程化TCR策略开发的启示。
To redirect T cells against tumor cells, T cells can be engineered ex vivo to express cancer-antigen specific T cell receptors (TCRs), generating products known as TCR-engineered T cells (TCR T). Unlike chimeric antigen receptors (CARs), TCRs recognize HLA-presented peptides derived from proteins of all cellular compartments.
The use of TCR T cells for adoptive cellular therapies (ACT) has gained increased attention, especially as efforts to treat solid cancers with ACTs have intensified. In this review, we describe the differing mechanisms of T cell antigen recognition and signal transduction mediated through CARs and TCRs.
We describe the classes of cancer antigens recognized by current TCR T therapies and discuss both classical and emerging pre-clinical strategies for antigen-specific TCR discovery, enhancement, and validation.
Finally, we review the current landscape of clinical trials for TCR T therapy and discuss what these current results indicate for the development of future engineered TCR approaches.
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