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通过优先积累红细胞锚定的载有趋化因子的纳米颗粒在肺转移部位来实现全身性肿瘤抑制。

Systemic tumour suppression via the preferential accumulation of erythrocyte-anchored chemokine-encapsulating nanoparticles in lung metastases.

机构信息

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.

出版信息

Nat Biomed Eng. 2021 May;5(5):441-454. doi: 10.1038/s41551-020-00644-2. Epub 2020 Nov 16.

Abstract

Eliciting immune responses against primary tumours is hampered by their immunosuppressive microenvironment and by the greater inaccessibility of deeper intratumoural cells. However, metastatic tumour cells are exposed to highly perfused and immunoactive organs, such as the lungs. Here, by taking advantage of the preferential colocalization of intravenously administered erythrocytes with metastases in the lungs, we show that treatment with chemokine-encapsulating nanoparticles that are non-covalently anchored onto the surface of injected erythrocytes results in local and systemic tumour suppression in mouse models of lung metastasis. Such erythrocyte-anchored systemic immunotherapy led to the infiltration of effector immune cells into the lungs, in situ immunization without the need for exogenous antigens, inhibition of the progression of lung metastasis, and significantly extended animal survival and systemic immunity that suppressed the growth of distant tumours after rechallenge. Erythrocyte-mediated systemic immunotherapy may represent a general and potent strategy for cancer vaccination.

摘要

针对原发性肿瘤的免疫反应受到其免疫抑制微环境和更深部肿瘤内细胞更难以接近的阻碍。然而,转移性肿瘤细胞暴露于高度灌注和免疫活性的器官,如肺部。在这里,我们利用静脉内给予的红细胞优先与肺部转移灶共定位的优势,表明用非共价锚定在注射红细胞表面的趋化因子包封纳米颗粒进行治疗可导致肺部转移的小鼠模型中的局部和全身肿瘤抑制。这种红细胞锚定的系统免疫疗法导致效应免疫细胞浸润肺部,无需外源性抗原的原位免疫,抑制肺转移的进展,并显著延长动物的存活时间和全身免疫力,在再次挑战后抑制远处肿瘤的生长。红细胞介导的系统免疫疗法可能代表一种用于癌症疫苗接种的通用且有效的策略。

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