Cancer Institute, The First Clinical Medical College, Xuzhou Medical University, Xuzhou, Jiangsu, P.R. China.
Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, P.R. China.
Cancer Immunol Res. 2023 Apr 3;11(4):515-529. doi: 10.1158/2326-6066.CIR-22-0531.
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.
共刺激结构域（CSD）的 4-1BB 和 CD28 是嵌合抗原受体（CAR）工程 T 细胞中最广泛使用的。这些 CAR T 细胞在治疗血液恶性肿瘤方面显示出令人鼓舞的疗效，但在实体瘤中的疗效有限。疱疹病毒进入介体（HVEM）是一种具有新型下游信号通路的共刺激分子。在针对靶细胞时，具有 HVEM CSD（HVEM-CAR T）的 CAR T 细胞在体外比 4-1BB-CAR T 或 CD28-CAR T 显示出更强的细胞因子释放和细胞毒性。此外，HVEM-CAR T 在几种小鼠肿瘤模型中显示出优越的治疗效果。从机制上讲，与基于 4-1BB 或 CD28 的 CAR T 细胞相比，HVEM CSD 赋予 CAR T 细胞减弱的耗竭、改善的功能和持久性，并增强了肿瘤组织中的代谢活性。这些研究表明，HVEM CSD 有可能提高 CAR T 细胞对实体瘤的治疗效果。
Cancer Discov. 2024-10-4
J Exp Clin Cancer Res. 2025-2-20
J Exp Clin Cancer Res. 2024-2-12
Zotero 插件