Division of Virology, Innsbruck Medical University, Innsbruck, Austria.
J Virol. 2011 Jun;85(11):5679-84. doi: 10.1128/JVI.02511-10. Epub 2011 Mar 30.
Vesicular stomatitis virus (VSV)-based oncolytic virotherapy has the potential to significantly improve the prognosis of aggressive malignancies such as brain cancer. However, VSV's inherent neurotoxicity has hindered clinical development so far. Given that this neurotropism is attributed to the glycoprotein VSV-G, VSV was pseudotyped with the nonneurotropic envelope glycoprotein of the lymphocytic choriomeningitis virus (LCMV-GP→VSV-GP). Compared to VSV, VSV-GP showed enhanced infectivity for brain cancer cells in vitro while sparing primary human and rat neurons in vitro and in vivo, respectively. In conclusion, VSV-GP has a much wider therapeutic window than VSV and is thus more suitable for clinical applications, especially in the brain.
基于水疱性口炎病毒（VSV）的溶瘤病毒治疗具有显著改善侵袭性恶性肿瘤（如脑癌）预后的潜力。然而，VSV 的固有神经毒性迄今为止一直阻碍其临床开发。鉴于这种嗜神经性归因于糖蛋白 VSV-G，VSV 被用淋巴细胞性脉络丛脑膜炎病毒（LCMV-GP→VSV-GP）的非神经毒性包膜糖蛋白进行了假型化。与 VSV 相比，VSV-GP 在体外对脑癌细胞的感染性增强，而分别在体外和体内对原代人源和大鼠神经元具有保护作用。总之，VSV-GP 的治疗窗口比 VSV 宽得多，因此更适合临床应用，尤其是在脑部。
