Glioblastoma (GBM) is an aggressive and common form of central nervous system primary malignant tumor in adults. GBM accounts for about half of all gliomas. Despite maximal resection, radiotherapy, and temozolomide, median survival is still 12–15 months because of tumor heterogeneity, diffuse infiltration, and therapeutic resistance. Recurrence is nearly universal, underscoring the need for novel therapies. Oncolytic virotherapy demonstrates a promising strategy that combines direct tumor cell lysis with immune activation. Tumor-selective viruses replicate within malignant cells, induce cell death, and release tumor antigens, thereby reshaping the immunosuppressive microenvironment. Several viral backbones have advanced to clinical testing, including adenovirus (DNX-2401), herpes simplex virus (G47Δ, G207), poliovirus (PVS-RIPO), measles virus (MV-CEA), reovirus (pelareorep), vaccinia virus (Pexa-Vec), and vesicular stomatitis virus (VSV-GP). The approval of G47Δ in Japan for malignant glioma marks a milestone, with early trials demonstrating safety and signals of durable benefit, particularly in combination regimens. Current research emphasizes engineering viral genomes to enhance selectivity, immune stimulation, and resistance to clearance, while exploring synergistic combinations with radiotherapy, chemotherapy, immune checkpoint inhibitors, and tumor-treating fields. Advances in delivery, such as convection-enhanced infusion and blood–brain barrier modulation, are also under investigation. Despite obstacles, oncolytic virotherapy holds significant potential within multimodal GBM strategies.
胶质母细胞瘤（GBM）是成人中枢神经系统最常见且具有高度侵袭性的原发性恶性肿瘤，约占所有胶质瘤病例的半数。尽管采用最大范围手术切除联合放疗及替莫唑胺治疗，但由于肿瘤异质性、弥漫性浸润及治疗抵抗等因素，患者中位生存期仍仅为12-15个月。该疾病几乎普遍复发，凸显了对新型疗法的迫切需求。溶瘤病毒疗法展现出极具前景的治疗策略，其通过直接裂解肿瘤细胞与激活免疫应答双重机制发挥作用。肿瘤选择性病毒在恶性细胞内复制并诱导细胞死亡，同时释放肿瘤抗原，从而重塑免疫抑制微环境。目前已有多种病毒载体进入临床试验阶段，包括腺病毒（DNX-2401）、单纯疱疹病毒（G47Δ、G207）、脊髓灰质炎病毒（PVS-RIPO）、麻疹病毒（MV-CEA）、呼肠孤病毒（pelareorep）、痘苗病毒（Pexa-Vec）以及水疱性口炎病毒（VSV-GP）。其中G47Δ在日本获批用于恶性胶质瘤治疗具有里程碑意义，早期临床试验已证实其安全性，并显示出持久疗效的积极信号，尤其在联合治疗方案中表现突出。当前研究重点聚焦于通过病毒基因组工程化改造提升其靶向选择性、免疫刺激能力及抗清除特性，同时积极探索与放疗、化疗、免疫检查点抑制剂及肿瘤治疗电场等疗法的协同组合方案。在递送技术方面，对流增强输注及血脑屏障调控等创新方法也正处于研究阶段。尽管面临诸多挑战，溶瘤病毒疗法在多模式GBM治疗策略中仍具有显著潜力。
The Emerging Role of Oncolytic Virotherapy in Glioblastoma Management
肿瘤(癌症)患者之家