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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:PD1CD28 chimeric molecule enhances EGFRvⅢ specific CAR-T cells in xenograft experiments in mouse models.
PD1CD28 chimeric molecule enhances EGFRvⅢ specific CAR-T cells in xenograft experiments in mouse models.
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多年来,CAR-T 细胞治疗在血液系统恶性肿瘤治疗中取得了显著成功,但在胶质母细胞瘤(GBM)中尚未重现这一疗效。本研究将 PD1CD28 嵌合分子导入靶向 EGFRv 的 CAR-T 细胞,构建 EGFRv-P2A-PD1CD28 CAR-T 细胞。值得注意的是,这一改造显著增加 IL-2 分泌,并增强 CAR-T 细胞的抗原依赖性激活,尤其是在体外存在程序性死亡配体 1(PD-L1)时。此外,体内异种移植实验显示,PD1CD28 嵌合分子对于降低复发率、有效控制复发肿瘤体积并最终延长小鼠生存期发挥了关键作用。总体而言,这些发现提示,共表达 PD1CD28 嵌合分子的 EGFRv 靶向 CAR-T 细胞有望显著提高 GBM 治疗效果。
Over the years, CAR-T cell therapy has achieved remarkable success in treating hematological malignancies.
However, this efficacy has not been replicated in the context of glioblastoma (GBM). In this study, a PD1CD28 chimeric molecule was introduced into EGFRv -directed CAR-T cells, generating EGFRv -P2A-PD1CD28 CAR-T cells.
Notably, this modification significantly increased IL-2 secretion and enhanced antigen-dependent activation of CAR-T cells, especially when programmed cell death ligand 1 (PD-L1) was present in vitro.
In addition, the in vivo xenograft experiments revealed that the PD1CD28 chimeric molecule played a pivotal role in reducing recurrence rates, effectively controlling recurrent tumor volume, and ultimately prolonging the survival of mice. Collectively, these findings suggest that EGFRv -directed CAR-T cells co-expressing the PD1CD28 chimeric molecule have the potential to significantly enhance the treatment efficacy against GBM.
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