School of Life Sciences, Jiangsu University, Zhenjiang, 212013, China.
Department of Gastroenterology, Suqian First People's Hospital, Suqian, 223800, Jiangsu, China.
Hum Cell. 2024 May;37(3):571-581. doi: 10.1007/s13577-024-01040-7. Epub 2024 Mar 4.
Chimeric antigen receptor (CAR) T-cell therapy is a new and innovative approach to treating cancers that has shown promising results in the treatment of lymphoma. However, it has been found to be less effective in the treatment of solid tumors. To overcome the limitation, researchers have explored the use of combined CAR-T therapy with other complementary regimens that target specific genes or biomarkers, which would enhance the synergistic therapeutic effects. Transcription factors (TFs) have been identified as potential markers that can regulate gene expression in CAR-T cells to enhance their cytotoxicity and safety. TFs are known to bind DNA specifically and recruit cofactor proteins to regulate the expression of target genes. By targeting TFs, it is possible to improve the anti-tumor response of CAR-T cells by altering their phenotype and transcriptional map, thereby increasing their effector function, such as reducing the exhaustion, enhancing the survival, and cytotoxicity of CAR-T cells. This review summarizes the application of transcription factors in CART therapy to enhance the synergistic therapeutic effect of CAR-T cells in the treatment of solid tumors and improve their anti-tumor responses.
嵌合抗原受体 (CAR) T 细胞疗法是一种治疗癌症的新方法，在淋巴瘤的治疗中显示出了有前途的结果。然而，它在治疗实体瘤方面的效果较差。为了克服这一限制，研究人员探索了将 CAR-T 疗法与其他针对特定基因或生物标志物的互补方案联合使用，以增强协同治疗效果。转录因子 (TFs) 已被确定为潜在的标志物，可调节 CAR-T 细胞中的基因表达，以增强其细胞毒性和安全性。TFs 特异性结合 DNA 并募集辅助因子蛋白来调节靶基因的表达。通过靶向 TFs，可以通过改变 CAR-T 细胞的表型和转录图谱来改善其抗肿瘤反应，从而增加其效应功能，例如减少 CAR-T 细胞的耗竭、增强其存活和细胞毒性。这篇综述总结了转录因子在 CART 治疗中的应用，以增强 CAR-T 细胞在治疗实体瘤中的协同治疗效果，并改善其抗肿瘤反应。
