1Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio.
2Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota; and.
Neurosurg Focus. 2021 Feb;50(2):E2. doi: 10.3171/2020.11.FOCUS20854.
High-grade gliomas (HGGs) inevitably recur and progress despite resection and standard chemotherapies and radiation. Viral therapies have emerged as a theoretically favorable adjuvant modality that might overcome intrinsic factors of HGGs that confer treatment resistance.
The authors present the results of systematic searches of the MEDLINE and ClinicalTrials.gov databases that were performed for clinical trials published or registered up to July 15, 2020.
Fifty-one completed clinical trials were identified that made use of a virus-based therapeutic strategy to treat HGG. The two main types of viral therapies were oncolytic viruses and viral vectors for gene therapy. Among clinical trials that met inclusion criteria, 20 related to oncolytic viruses and 31 to gene therapy trials. No oncolytic viruses have progressed to phase III clinical trial testing, although there have been many promising early-phase results and no reported cases of encephalitis or death due to viral therapy. Three phase III trials in which viral gene therapy was used have been completed but have not resulted in any FDA-approved therapy. Recent efforts in this area have been focused on the delivery of suicide genes such as herpes simplex virus thymidine kinase and cytosine deaminase.
Decades of research efforts and an improving understanding of the immunomodulatory effects of viral therapies for gliomas are informing ongoing clinical efforts aimed at improving outcomes in patients with HGG. The available clinical data reveal varied efficacy among different virus-based treatment strategies.
尽管进行了手术切除和标准的化疗及放疗，高级别胶质瘤（HGG）仍不可避免地复发和进展。病毒疗法已成为一种理论上有利的辅助治疗模式，可能克服赋予 HGG 治疗抵抗性的内在因素。
作者对截至 2020 年 7 月 15 日发表或注册的临床试验进行了 MEDLINE 和 ClinicalTrials.gov 数据库的系统检索。
确定了 51 项完成的临床试验，这些试验利用基于病毒的治疗策略治疗 HGG。两种主要类型的病毒疗法是溶瘤病毒和用于基因治疗的病毒载体。在符合纳入标准的临床试验中，有 20 项与溶瘤病毒相关，31 项与基因治疗试验相关。尽管有许多有前途的早期结果，并且没有因病毒治疗而导致脑炎或死亡的报告，但没有一种溶瘤病毒进展到 III 期临床试验测试。已经完成了三项使用病毒基因治疗的 III 期试验，但没有一种疗法获得 FDA 批准。该领域的最新研究重点是递送自杀基因，如单纯疱疹病毒胸苷激酶和胞嘧啶脱氨酶。
几十年来，对病毒疗法治疗胶质瘤的免疫调节作用的研究努力和认识的提高，为旨在改善 HGG 患者结局的正在进行的临床努力提供了信息。现有的临床数据显示，不同基于病毒的治疗策略的疗效存在差异。
