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通过修饰细胞表面,用靶向适配体工程化 M1 巨噬细胞以增强过继免疫治疗

英文原题:Engineering M1 macrophages with targeting aptamers for enhanced adoptive immunotherapy by modifying the cell surface.

查看英文原题

Engineering M1 macrophages with targeting aptamers for enhanced adoptive immunotherapy by modifying the cell surface.

PubMed 2024/07/03(内容时间) Biomed Pharmacother

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中文摘要

巨噬细胞通过吞噬肿瘤细胞、呈递抗原和激活适应性T细胞,在机体防御癌症中发挥关键作用。然而,巨噬细胞本身无法递送靶向癌症免疫疗法。工程化过继细胞疗法通过改造巨噬细胞,增强细胞的先天免疫反应并提高临床疗效,从而引入新的靶向和抗肿瘤能力。在本研究中,我们开发了工程化巨噬细胞胆固醇-AS1411-M1(CAM1)用于细胞免疫治疗。为了靶向巨噬细胞,将胆固醇-AS1411适配体锚定在M1巨噬细胞表面以制备CAM1,无需基因修饰或细胞损伤。在小鼠乳腺癌细胞中,CAM1诱导的凋亡/死亡率显著高于未修饰的M1巨噬细胞。将AS1411锚定在巨噬细胞表面为构建用于肿瘤免疫治疗的工程化巨噬细胞提供了一种新方法。

展开英文摘要原文

Macrophages play a critical role in the body's defense against cancer by phagocytosing tumor cells, presenting antigens, and activating adaptive T cells.

However, macrophages are intrinsically incapable of delivering targeted cancer immunotherapies. Engineered adoptive cell therapy introduces new targeting and antitumor capabilities by modifying macrophages to enhance the innate immune response of cells and improve clinical efficacy. In this study, we developed engineered macrophage cholesterol-AS1411-M1 (CAM1) for cellular immunotherapy.

To target macrophages, cholesterol-AS1411 aptamers were anchored to the surface of M1 macrophages to produce CAM1 without genetic modification or cell damage. CAM1 induced significantly higher apoptosis/mortality than unmodified M1 macrophages in murine breast cancer cells. Anchoring AS1411 on the surface of macrophages provided a novel approach to construct engineered macrophages for tumor immunotherapy.

论文信息

作者
Yang Q、Hu S、Wang Y、Zhong L、Yu X、Zhang Y、Du X、Wang S
第一作者单位
School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.China
通讯作者单位
School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China. Electronic address: tianqc@hznu.edu.cn.China
期刊
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2024 Aug
原文标识
PubMed 38964179 · DOI 10.1016/j.biopha.2024.117064