前沿| 耶鲁年夜学发明埃玻拉病毒能断根胶质母细胞瘤术中残留肿瘤细胞

关在医治胶质母细胞瘤的新发明。

作者： 本站编纂来历： 神外前沿2020-02-19 10:58:07

据yalenews报导，胶质母细胞瘤（GBM）是一种极具侵袭性的脑肿瘤。

日前，来自耶鲁年夜学的一个团队带来了于该范畴的一项冲破，发明埃玻拉病毒的身分将带来一种有但愿的新疗法，该疗法已经经于试验鼠中被证实能杀逝世胶质母细胞瘤。该研究陈诉已经揭晓于《Journal of Virology》上。

据相识，胶质母细胞瘤患者的尺度医治要领是先经由过程手术摘除了肿瘤，然落伍行化疗以及放疗从而杀失所有残留的癌细胞。问题是，这些溜走的细胞常常会逃到脑构造中躲于那里并又很快地孕育发生新的肿瘤，且照旧致命的。

半个多世纪以来，科学家们始终于起劲设计具备靶向性并能杀逝世癌细胞的病毒。2017年的一项研究显示，寨卡病毒可以被用来进犯胶质母细胞瘤。

这类要领的暗地里逻辑是经由过程癌细胞对于外来威逼的反映来睁开，当病原体或者其他入侵者对于人体倡议进犯时，一般的康健细胞会触发免疫反映举行防备，而年夜大都癌细胞没法做到这一点。是以，用病毒进犯癌细胞可以哄骗这一弱点，而使康健细胞基本上不受危险。

埃玻拉病毒则是一个出格有远景的候选病毒。于神经外科传授Anthony N. Van den Pol的领导下，耶鲁年夜学的研究小组始终于研究这类病毒的组成，但愿能更好地哄骗它傍边的一些强盛东西。于此历程中，他们发明了一个具备两种可取属性的单一基因，它既能帮忙病毒回避人体的免疫反映，如许它就能有用地完成它的事情，又能于病毒的致命性中阐扬作用，如许它就能进犯癌细胞）。

科学家们将这类基因转化成一种嵌合病毒--该病毒由多种病毒的基因组合组成。这类嵌合病毒被打针到患有胶质母细胞瘤的老鼠的年夜脑中，研究小组发明从埃玻拉病毒中提取的基因使其可以或许选择性地对准并捣毁脑肿瘤。

以上部门内容来历cnBeta.COM，英文原文报导链接为：

https://news.yale.edu/2020/02/12/scientists-find-ally-fight-against-brain-tumors-ebola

附录：Journal of Virology 英文论文择要

Mucin-like domain of Ebola virus glycoprotein enhances selective oncolytic actions against brain tumors

ABSTRACT

Given that the Ebola virus (EBOV) infects a wide array of organs and cells yet displays a relative lack of neurotropism, we asked whether a chimeric vesicular stomatitis virus (VSV) expressing the EBOV glycoprotein (GP) might selectively target brain tumors. The mucin-like domain (MLD) of the EBOV GP may enhance virus i妹妹une system evasion. Here we compare chimeric VSVs in which EBOV GP replaces the VSV glycoprotein, thereby reducing the neurotoxicity associated with wildtype VSV. A chimeric VSV expressing the full-length EBOV GP (VSV-EBOV) containing the MLD was substantially more effective and safer than a parallel construct with an EBOV GP lacking the MLD (VSV-EBOVΔMLD). One-step growth, RT-qPCR, and Western blot assessment showed VSV-EBOVΔMLD produced substantially more progeny faster than VSV-EBOV. Using i妹妹unodeficient SCID mice, we focused on targeting human brain tumors with these VSV-EBOVs. Similar to our previous report using an attenuated VSV-EBOV with no MLD that expressed GFP (VSV-EBOVΔMLD-GFP), VSV-EBOVΔMLD without GFP targeted glioma, but yielded only a modest extension of survival. In contrast, VSV-EBOV containing the MLD showed substantially better targeting and elimination of brain tumors after intravenous delivery, and increased the survival of brain tumor-bearing mice. Despite the apparent destruction of most tumor cells by VSV-EBOVΔMLD, the virus remained active within the SCID mouse brain and showed widespread infection of normal brain cells. In contrast, VSV-EBOV eliminated the tumors, and showed relatively little infection of normal brain cells. Parallel experiments with direct intracranial virus infection generated similar results. Neither VSV-EBOV nor VSV-EBOVΔMLD showed substantive infection of the brains of normal i妹妹unocompetent mice.

Importance. The Ebola virus glycoprotein contains a mucin-like domain which may play a role in i妹妹une evasion. Chimeric vesicular stomatitis viruses with the EBOV glycoprotein substituted for the VSV glycoprotein show greater safety and efficacy in targeting brain tumors in i妹妹unodeficient mice when the MLD is expressed within the EBOV glycoprotein compared with EBOV lacking the mucin-like domain.

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