ETH Zurich, Department of Biosystems Science and Engineering, Basel, Switzerland.
ETH Zurich, Department of Biosystems Science and Engineering, Basel, Switzerland.
Trends Biotechnol. 2021 Dec;39(12):1308-1320. doi: 10.1016/j.tibtech.2021.03.005. Epub 2021 Apr 5.
Chimeric antigen receptor (CAR)-T cell therapies against cancer continue to make inroads in the clinic. However, progress is still hindered by subpar efficacy against many tumors. Gaining a better understanding of CAR-induced T cell activation would help identify and remediate the causes of treatment failure. Increasingly, technologies to analyze the transcriptome are used to molecularly profile the behavior of CAR-T cells, both before and after treatment. Here, we describe recent work on how gene expression signatures, especially those obtained from single-cell RNA sequencing (scRNA-seq), can be used to characterize CAR design, production conditions, therapy combinations, and finally disease outcome. In the future, scRNA-seq could become a standard tool for the development and clinical monitoring of CAR-T cell therapies.
嵌合抗原受体 (CAR)-T 细胞疗法在临床上的应用不断取得进展。然而,许多肿瘤的疗效仍然欠佳,阻碍了这一疗法的发展。更好地了解 CAR 诱导的 T 细胞激活将有助于识别和纠正治疗失败的原因。越来越多的分析转录组的技术被用于对 CAR-T 细胞的行为进行分子分析,包括治疗前后。在这里,我们描述了最近在如何使用基因表达特征(尤其是单细胞 RNA 测序 (scRNA-seq) 获得的特征)来描述 CAR 设计、生产条件、治疗组合,最后是疾病结果方面的工作。在未来,scRNA-seq 可能成为 CAR-T 细胞疗法的开发和临床监测的标准工具。