医学分子生物学杂志2026，Vol.23Issue(5)：477-484,8.DOI:10.3870/j.issn.1672-8009.2026.05.001
胞内信号结构优化的BCMA-E-CAR-T细胞功能与安全性
Functions and Safety of Intracellular Structure-Optimized BCMA-E-CAR-T Cells
摘要
Abstract
Objective To construct CAR-T cells harboring distinct intracellular signaling domains,thereby addressing the core limitations of conventional CAR-T cells,including premature exhaustion,insufficient antitumor efficacy,and uncontrolled cytokine release syndrome caused by excessive intracellular activation signals.Methods The intracellular signaling domain CD3ζ of the conventional CAR construct was replaced with the CD3ε signaling domain containing only one immu-noreceptor tyrosine-based activation motif(ITAM),to generate a novel BCMA-E-CAR-T cell prod-uct.Flow cytometry was employed to assess the cytotoxicity against target cells,activation status,exhaustion profile,central memory phenotype differentiation,proliferative capacity,and cytokine secretion levels of the engineered CAR-T cells.Results BCMA-E-CAR-T cells exhibited signifi-cantly enhanced cytotoxicity against target cells,accompanied by reduced activation levels,allevi-ated exhaustion,diminished cytokine release,elevated differentiation toward a central memory phe-notype,and stronger proliferative potential.Conclusion This study successfully constructed novel BCMA-E-CAR-T cells harboring CD3ε as the intracellular activation signaling domain,which exhib-ited significantly enhanced antitumor activity and improved therapeutic safety in tumor models.关键词
嵌合抗原受体T细胞/B细胞成熟抗原/CD3ε/免疫受体酪氨酸激活基序/细胞因子释放综合征/耗竭Key words
CAR-T/B-cell maturation antigen/CD3ε/immune receptor tyrosine activation motif/exhaustion/cytokine release syndrome分类
医药卫生引用本文复制引用
李琰龙,王鹏举,张仪婷,秦炜炜,杨安钢,阎博..胞内信号结构优化的BCMA-E-CAR-T细胞功能与安全性[J].医学分子生物学杂志,2026,23(5):477-484,8.基金项目
陕西省卫生健康科研创新平台(No.2025PT-07),陕西省重点项目-实验室重点项目(No.2025SYS-SYSZD-030) This work was supported by grants from the Health Research and Innovation Platform of Shaanxi Provincial Health Commission(No.2025PT-07),the Key Project of Shaanxi Province-Laboratory Key Project(No.2025SYS-SYSZD-030). （No.2025PT-07）
