High-grade gliomas—particularly glioblastoma (GBM)—remain refractory to standard-of-care surgery followed by chemoradiation, with a median overall survival of ~15 months. Oncolytic viruses (OVs), which selectively infect and lyse tumor cells while engaging antitumor immunity, offer a mechanistically distinct therapeutic modality. This review synthesizes clinical progress of OVs in GBM, with emphasis on oncolytic herpes simplex virus (oHSV) and coverage of other vectors (adenovirus, reovirus, Newcastle disease virus, vaccinia virus) across phase I–III trials, focusing on efficacy and safety. Key observations include the encouraging clinical trajectory of oHSV exemplars—T-VEC (approved for melanoma) and G47Δ (approved in Japan for recurrent GBM)—the multi-center exploration of the adenovirus DNX-2401 combined with programmed death-1 (PD-1) blockade, and the early-stage status of reovirus (pelareorep) and Newcastle disease virus programs. Emerging evidence indicates that oHSV therapy augments immune infiltration within the tumor microenvironment and alleviates immunosuppression, with synergy when combined with chemotherapy or immune checkpoint inhibitors. Persistent challenges include GBM’s inherently immunosuppressive milieu, limitations imposed by the blood–brain barrier, intrapatient viral delivery and biodistribution, and concerns about viral shedding. Future directions encompass programmable vector design, optimization of systemic delivery, biomarker-guided patient selection, and rational combination immunotherapy. Collectively, OVs represent a promising immunotherapeutic strategy in GBM; further gains will hinge on vector engineering and precision combinations to translate mechanistic promise into durable clinical benefit.
高级别胶质瘤——尤其是胶质母细胞瘤（GBM）——对标准治疗方案（手术联合放化疗）仍难以产生有效应答，患者中位总生存期仅约15个月。溶瘤病毒（OVs）作为一种机制独特的治疗手段，能够选择性感染并裂解肿瘤细胞，同时激活抗肿瘤免疫应答。本综述系统梳理了溶瘤病毒在胶质母细胞瘤领域的临床进展，重点阐述溶瘤性单纯疱疹病毒（oHSV）的临床应用，并涵盖其他载体（腺病毒、呼肠孤病毒、新城疫病毒、痘苗病毒）在I-III期临床试验中的疗效与安全性数据。核心发现包括：已获批黑色素瘤适应症的T-VEC及在日本获批治疗复发性GBM的G47Δ等oHSV制剂展现出积极的临床发展态势；腺病毒载体DNX-2401联合程序性死亡受体-1（PD-1）阻断剂的多中心研究取得进展；而呼肠孤病毒（pelareorep）与新城疫病毒项目尚处早期研发阶段。最新证据表明，oHSV疗法能增强肿瘤微环境内的免疫细胞浸润并缓解免疫抑制状态，与化疗或免疫检查点抑制剂联用可产生协同效应。当前面临的持续挑战包括：GBM固有的免疫抑制微环境、血脑屏障的限制、患者体内病毒递送与生物分布问题以及病毒脱落风险。未来发展方向涵盖可编程载体设计、全身给药方案优化、生物标志物指导的患者筛选以及合理的联合免疫治疗策略。总体而言，溶瘤病毒在GBM治疗中展现出广阔的免疫治疗前景；其进一步发展将取决于载体工程技术的突破与精准联合治疗方案的构建，从而将机制优势转化为持久的临床获益。
肿瘤(癌症)患者之家