神外前沿訊，據yalenews報導，膠質母細胞瘤（GBM）是一種極具侵襲性的腦腫瘤。日前，來自耶魯大學的一個團隊帶來了在該領域的一項突破，發現伊波拉病毒的成分將帶來一種有希望的新療法，該療法已經在實驗鼠中被證明能殺死膠質母細胞瘤。該研究報告已發表在《Journal of Virology》上。
據了解，膠質母細胞瘤患者的標準治療方法是先通過手術摘除腫瘤，然後進行化療和放療從而殺掉所有殘留的癌細胞。問題是，這些溜走的細胞經常會逃到腦組織中躲在那裡並又很快地產生新的腫瘤，且還是致命的。
半個多世紀以來，科學家們一直在努力設計具有靶向性並能殺死癌細胞的病毒。2017年的一項研究顯示，寨卡病毒可以被用來攻擊膠質母細胞瘤。
這種方法的背後邏輯是通過癌細胞對外來威脅的反應來展開，當病原體或其他入侵者對人體發起攻擊時，正常的健康細胞會觸發免疫反應進行防禦，而大多數癌細胞無法做到這一點。因此，用病毒攻擊癌細胞可以利用這一弱點，而使健康細胞基本上不受傷害。
伊波拉病毒則是一個特別有前景的候選病毒。在神經外科教授Anthony N. Van den Pol的帶領下，耶魯大學的研究小組一直在研究這種病毒的構成，希望能更好地利用它當中的一些強大工具。在此過程中，他們發現了一個具有兩種可取屬性的單一基因，它既能幫助病毒逃避人體的免疫反應，這樣它就能有效地完成它的工作，又能在病毒的致命性中發揮作用，這樣它就能攻擊癌細胞）。
科學家們將這種基因轉化成一種嵌合病毒--該病毒由多種病毒的基因組合構成。這種嵌合病毒被注射到患有膠質母細胞瘤的老鼠的大腦中，研究小組發現從伊波拉病毒中提取的基因使其能夠選擇性地瞄準並摧毀腦腫瘤。
以上部分內容來源cnBeta.COM，英文原文報導連結為：https://news.yale.edu/2020/02/12/scientists-find-ally-fight-against-brain-tumors-ebola
附錄：Journal of Virology 英文論文摘要
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.
論文原文連結：https://jvi.asm.org/content/early/2020/02/06/JVI.01967-19
相關報導：
精品課件| 溶瘤病毒與腦膠質瘤分子生物學進展-天壇醫院劉福生
神外前沿-科技推動學科進步，投稿郵箱 shenwaiqianyan@qq.com