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带有抗转铁蛋白受体抗体的 T 细胞来源细胞外囊泡用于多癌靶向

英文原题:T-Cell-Derived Extracellular Vesicles with an Antitransferrin Receptor Antibody for Multicancer Targeting.

查看英文原题

T-Cell-Derived Extracellular Vesicles with an Antitransferrin Receptor Antibody for Multicancer Targeting.

PubMed 2025/07/15(内容时间) Nano Lett Q1 · IF 9.1(JCR 2025)

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中文摘要

近期研究探索了免疫细胞来源的小细胞外囊泡(sEVs)的抗癌特性,但仍存在许多挑战,如需要改善靶向性等。为应对这些挑战,我们工程化改造了携带抗转铁蛋白受体1(TfR1)抗体的T细胞来源sEVs(T-EVs)。通过流式细胞术、免疫细胞化学、活细胞成像和体外阻断实验证实,该修饰增强了sEV对六种癌细胞的递送。T-EVs还降低了PD-L1和Rab27a水平,减少了乳腺癌细胞sEV的产生,并增加了对CD8+ T细胞介导的细胞毒作用的敏感性。全身给药的T-EVs在小鼠模型中有效靶向乳腺、肺和皮肤肿瘤。值得注意的是,T-EVs显著抑制了肿瘤生长,且无全身毒性。此外,T-EVs降低了癌细胞中PD-L1和Rab27a水平,同时增强了CD8+ T细胞的细胞毒性和增殖。总体而言,本研究强调了T-EVs对多种癌症类型的抗癌作用,凸显了其在开发靶向癌症疗法方面的潜力。

展开英文摘要原文

Recent research has explored the anticancer properties of immune-cell-derived small extracellular vesicles (sEVs), but many challenges, like the need for improved targeting, remain. To address these challenges, we engineered T-cell-derived sEVs with antitransferrin receptor 1 (TfR1) antibodies (T-EVs).

This modification enhanced the delivery of sEV to six types of cancer cells, as confirmed by flow cytometry, immunocytochemistry, live cell imaging, and blocking experiments in vitro . The T-EVs also reduced PD-L1 and Rab27a levels, decreased sEV production from breast cancer cells, and increased susceptibility to CD8 + T-cell-mediated cytotoxicity. Systemically administered T-EVs efficiently targeted breast, lung, and skin tumors in mouse models.

Notably, T-EVs significantly inhibited tumor growth without systemic toxicity.

Additionally, T-EVs reduced PD-L1 and Rab27a levels in cancer cells while enhancing the CD8 + T-cell cytotoxicity and proliferation.

Overall, this study highlights the anticancer effects of T-EVs against multiple cancer types, underscoring their potential in developing targeted cancer therapies.

论文信息

作者
Cho H、Ju H、Shin S、Ahn Y、Park E、Jung I、Kang SM、Noh S
第一作者单位
Department of Biomedical Science, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.South Korea
通讯作者单位
Department of Molecular Medicine, CMRI, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.South Korea
文献类型
美国 NIH 院内研究 · 非美国政府资助研究
期刊
Nano letters2025 Jul 23
原文标识
PubMed 40662672 · DOI 10.1021/acs.nanolett.5c01830