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PD1CD28 嵌合分子在小鼠模型异种移植实验中增强 EGFRvⅢ 特异性 CAR-T 细胞

英文原题:PD1CD28 chimeric molecule enhances EGFRvⅢ specific CAR-T cells in xenograft experiments in mouse models.

查看英文原题

PD1CD28 chimeric molecule enhances EGFRvⅢ specific CAR-T cells in xenograft experiments in mouse models.

PubMed 2024/10/01(内容时间) PLoS One Q2 · IF 2.8(JCR 2025)

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中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Chen W、Xian N、Zhao N、Zhang Q、Xu Y
第一作者单位
School of Pharmacy, Quanzhou Medical College, Quanzhou, Fujian, China.China
通讯作者单位
Laboratory of Snake Venom, The Center of Translational Hematology, Fujian Medical University, Fuzhou, Fujian, China.China
期刊
PloS one2024
原文标识
PubMed 39352918 · DOI 10.1371/journal.pone.0310430