CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
疱疹病毒侵入介体共刺激信号通过代谢重编程增强 CAR-T 细胞对实体瘤的疗效
英文原题：Herpes Virus Entry Mediator Costimulation Signaling Enhances CAR T-cell Efficacy Against Solid Tumors Through Metabolic Reprogramming.
查看英文原题
Herpes Virus Entry Mediator Costimulation Signaling Enhances CAR T-cell Efficacy Against Solid Tumors Through Metabolic Reprogramming.
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中文摘要
4-1BB和CD28的共刺激结构域（CSD）是嵌合抗原受体（CAR）工程化T细胞中应用最广泛的结构。此类CAR-T 细胞治疗血液系统恶性肿瘤的疗效令人鼓舞，但治疗实体瘤的效果有限。疱疹病毒入侵介质（HVEM）是一种具有新型下游信号通路的共刺激分子。面对靶细胞时，具有HVEM CSD的CAR-T 细胞（HVEM-CAR-T）在体外释放细胞因子和发挥细胞毒性的能力均强于4-1BB-CAR-T 或CD28-CAR-T。此外，在多种小鼠肿瘤模型中，HVEM-CAR-T 显示出更优的治疗效果。机制上，与基于4-1BB或CD28的CAR-T 细胞相比，HVEM CSD使CAR-T 细胞在肿瘤组织中的耗竭减轻、功能和持久性改善、代谢活性增强。本研究表明，HVEM CSD有望提高CAR-T 细胞治疗实体瘤的疗效。
展开英文摘要原文
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.
论文信息
- 作者
- Sun S、Huang C、Lu M、Xu H、Yuan Y、Zhao W、Hu X、Wang B
- 单位
- Cancer Institute, The First Clinical Medical College, Xuzhou Medical University, Xuzhou, Jiangsu, P.R. China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Cancer immunology research2023 Apr 3
- 原文标识
- PubMed 36689620 · DOI 10.1158/2326-6066.CIR-22-0531