Goetz Christian, Dobrikova Elena, Shveygert Mayya, Dobrikov Mikhail, Gromeier Matthias
Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Future Virol. 2011 Sep;6(9):1045-1058. doi: 10.2217/fvl.11.76.
In cancerous cells, physiologically tight regulation of protein synthesis is lost, contributing to uncontrolled growth and proliferation. We describe a novel experimental cancer therapy approach based on genetically recombinant poliovirus that targets an intriguing aberration of translation control in malignancy. This strategy is based on the confluence of several factors enabling specific and efficacious cancer cell targeting. Poliovirus naturally targets the vast majority of ectodermal/neuroectodermal cancers expressing its cellular receptor. Evidence from glioblastoma patients suggests that the poliovirus receptor is ectopically upregulated on tumor cells and may be associated with stem cell-like cancer cell populations and proliferating tumor vasculature. We exploit poliovirus' reliance on an unorthodox mechanism of protein synthesis initiation to selectively drive viral translation, propagation and cytotoxicity in glioblastoma. PVSRIPO, a prototype nonpathogenic poliovirus recombinant, is scheduled to enter clinical investigation against glioblastoma.
在癌细胞中，蛋白质合成的生理严格调控丧失，导致不受控制的生长和增殖。我们描述了一种基于基因重组脊髓灰质炎病毒的新型实验性癌症治疗方法，该病毒靶向恶性肿瘤中一种有趣的翻译控制异常。该策略基于几个因素的融合，能够实现特异性和有效的癌细胞靶向。脊髓灰质炎病毒天然靶向绝大多数表达其细胞受体的外胚层/神经外胚层癌症。来自胶质母细胞瘤患者的证据表明，脊髓灰质炎病毒受体在肿瘤细胞上异位上调，可能与干细胞样癌细胞群体和增殖的肿瘤血管有关。我们利用脊髓灰质炎病毒对非正统蛋白质合成起始机制的依赖，在胶质母细胞瘤中选择性地驱动病毒翻译、传播和细胞毒性。PVSRIPO是一种原型非致病性脊髓灰质炎病毒重组体，计划针对胶质母细胞瘤进行临床研究。
