前沿| 耶鲁大学发现埃博拉病毒能清除胶质母细胞瘤术中残留肿瘤细胞

关于治疗胶质母细胞瘤的新发现。

作者: 本站编辑 来源: 神外前沿 2020-02-19 10:58:07

据yalenews报道,胶质母细胞瘤(GBM)是一种极具侵袭性的脑肿瘤。

日前,来自耶鲁大学的一个团队带来了在该领域的一项突破,发现埃博拉病毒的成分将带来一种有希望的新疗法,该疗法已经在实验鼠中被证明能杀死胶质母细胞瘤。该研究报告已发表在《Journal of Virology》上。

据了解,胶质母细胞瘤患者的标准治疗方法是先通过手术摘除肿瘤,然后进行化疗和放疗从而杀掉所有残留的癌细胞。问题是,这些溜走的细胞经常会逃到脑组织中躲在那里并又很快地产生新的肿瘤,且还是致命的。

半个多世纪以来,科学家们一直在努力设计具有靶向性并能杀死癌细胞的病毒。2017年的一项研究显示,寨卡病毒可以被用来攻击胶质母细胞瘤。

这种方法的背后逻辑是通过癌细胞对外来威胁的反应来展开,当病原体或其他入侵者对人体发起攻击时,正常的健康细胞会触发免疫反应进行防御,而大多数癌细胞无法做到这一点。因此,用病毒攻击癌细胞可以利用这一弱点,而使健康细胞基本上不受伤害。

埃博拉病毒则是一个特别有前景的候选病毒。在神经外科教授Anthony N. Van den Pol的带领下,耶鲁大学的研究小组一直在研究这种病毒的构成,希望能更好地利用它当中的一些强大工具。在此过程中,他们发现了一个具有两种可取属性的单一基因,它既能帮助病毒逃避人体的免疫反应,这样它就能有效地完成它的工作,又能在病毒的致命性中发挥作用,这样它就能攻击癌细胞)。

科学家们将这种基因转化成一种嵌合病毒--该病毒由多种病毒的基因组合构成。这种嵌合病毒被注射到患有胶质母细胞瘤的老鼠的大脑中,研究小组发现从埃博拉病毒中提取的基因使其能够选择性地瞄准并摧毁脑肿瘤。

以上部分内容来源cnBeta.COM,英文原文报道链接为:

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

附录:Journal of Virology  英文论文摘要

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 immune 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 immunodeficient 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 immunocompetent mice.

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


耶鲁大学 埃博拉病毒 胶质母细胞瘤术

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