CD28
嵌合抗原受体
癌症研究
调解人
T细胞
免疫疗法
细胞生物学
免疫学
生物
免疫系统
作者
Shishuo Sun,Chao Huang,Mengmeng Lü,Heng Xu,Yifan Yuan,Wanxin Zhao,Xiaolei Hu,Bixi Wang,Wei Zhang,Xiaoge Gao,Junnian Zheng,Lishan Su,Qing Zhang
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2023-01-23
卷期号:11 (4): 515-529
被引量:5
标识
DOI:10.1158/2326-6066.cir-22-0531
摘要
Abstract Costimulatory domains (CSD) of 4-1BB and CD28 are most widely used in chimeric antigen receptor (CAR)–engineered T cells. These CAR T cells have shown encouraging efficacy in the treatment of hematologic malignancies but have limited efficacy in solid tumors. The herpes virus entry mediator (HVEM) is a costimulatory molecule with a novel downstream signaling pathway. In response to target cells, CAR T cells with a HVEM CSD (HVEM-CAR T) displayed more robust cytokine release and cytotoxicity than 4-1BB-CAR T or CD28-CAR T in vitro. Furthermore, HVEM-CAR T showed superior therapeutic efficacy in several mouse tumor models. Mechanistically, the HVEM CSD endowed CAR T cells with attenuated exhaustion, improved function and persistence, and enhanced metabolic activities in tumor tissue compared with 4-1BB–based or CD28-based CAR T cells. These studies establish that the HVEM CSD has the potential to improve the therapeutic efficacy of CAR T cells against solid tumors.
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