Department of Neurosurgery, Hospital of the University of Munich, Grosshadern, Munich, Germany.
Anticancer Res. 2012 Apr;32(4):1137-44.
Glioblastoma multiforme is a highly aggressive tumor with a median survival of 14 months despite all standard therapies. Focusing on alternative treatment strategies, we evaluated the oncolytic potential of varicella zoster virus (VZV) in malignant glioma cell cultures.
Replication of wildtype and mutant VZV was comparatively analyzed in glioma cell lines (U87, U251 and U373) and in primary malignant glioma cells (n=10) in vitro by infectious foci assay, immunofluorescence microscopy and western blot analysis. Additionally, the tumor-targeting potential of VZV-infected human mesenchymal stem cells was evaluated.
VZV replicated efficiently in all the glioma cells studied here followed by rapid oncolysis in vitro. The attenuated vaccine VZV mutant rOKA/ORF63rev[T171] exhibited most efficient replication. Human mesenchymal stem cells were found suitable for targeting VZV to sites of tumor growth.
VZV exhibits an intrinsic oncolytic potential in malignant glioma cell cultures and might be a novel candidate for virotherapy in glioblastoma multiforme.
多形性胶质母细胞瘤是一种高度侵袭性肿瘤，尽管采用了所有标准疗法，其中位生存期仍为 14 个月。我们专注于替代治疗策略，评估了水痘带状疱疹病毒（VZV）在恶性胶质瘤细胞培养物中的溶瘤潜力。
通过感染斑测定、免疫荧光显微镜和 Western blot 分析，比较分析野生型和突变型 VZV 在胶质瘤细胞系（U87、U251 和 U373）和原代恶性胶质瘤细胞（n=10）中的复制情况。此外，还评估了感染 VZV 的人间质干细胞的肿瘤靶向潜力。
VZV 在所有研究的胶质瘤细胞中均能有效复制，随后迅速在体外发生溶瘤。减毒疫苗 VZV 突变株 rOKA/ORF63rev[T171]表现出最高效的复制。人间质干细胞适合将 VZV 靶向肿瘤生长部位。
VZV 在恶性胶质瘤细胞培养物中具有内在的溶瘤潜力，可能是多形性胶质母细胞瘤病毒治疗的新候选药物。
