Soldozy Sauson, Eichberg Daniel G, Morell Alexis A, Luther Evan, Lu Victor M, Higgins Dominique M O, Patel Nitesh V, Shah Ashish H, Hanft Simon J, Komotar Ricardo J, Ivan Michael E
Department of Neurosurgery, Westchester Medical Center, New York Medical College, 100 Woods Road, Valhalla, New York, NY 10595, USA.
Department of Neurological Surgery, University of Miami, 1295 NW 14th St, Miami, FL 33125, USA.
Pathogens. 2023 Jun 22;12(7):861. doi: 10.3390/pathogens12070861.
Brain tumor incidence is on the rise, and glioblastoma comprises the majority of primary tumors. Despite maximal safe resection and adjuvant chemoradiation, median survival for high-grade glioma remains poor. For this reason, it is important to develop and incorporate new treatment strategies. Oncolytic virotherapy has emerged as a viable new therapeutic entity to fill this gap. Preclinical research has shown oncolytic virotherapy to be a robust and effective treatment option for brain tumors, and clinical trials for both adult and pediatric high-grade glioma are underway. The unique and protected environment of the nervous system, in part due to the blood-brain barrier, prevents traditional systemic therapies from achieving adequate penetration. Brain tumors are also heterogenous in nature due to their diverse molecular profiles, further complicating systemic treatment efforts. Oncolytic viruses may serve to fill this gap in brain tumor treatment given their amenability to genetic modification and ability to target unique tumor epitopes. In addition, direct inoculation of the oncolytic virus agent to the tumor bed following surgical resection absolves risk of systemic side effects and ensures adequate delivery. As virotherapy transitions from bench to bedside, it is important to discuss factors to make this transition more seamless. In this article, we describe the current clinical evidence as it pertains to oncolytic virotherapy and the treatment of brain tumors as well as factors to consider for its incorporation into neurosurgical workflow.
脑肿瘤的发病率正在上升,胶质母细胞瘤占原发性肿瘤的大多数。尽管进行了最大程度的安全切除和辅助放化疗,但高级别胶质瘤的中位生存期仍然很差。因此,开发并纳入新的治疗策略很重要。溶瘤病毒疗法已成为填补这一空白的可行新治疗手段。临床前研究表明,溶瘤病毒疗法是一种针对脑肿瘤的强大且有效的治疗选择,针对成人和儿童高级别胶质瘤的临床试验正在进行中。神经系统独特且受保护的环境,部分归因于血脑屏障,阻止了传统全身疗法实现充分渗透。脑肿瘤因其多样的分子特征在本质上也是异质性的,这进一步使全身治疗变得复杂。溶瘤病毒因其易于基因改造和靶向独特肿瘤表位的能力,可能有助于填补脑肿瘤治疗中的这一空白。此外,手术切除后将溶瘤病毒制剂直接接种到肿瘤床可消除全身副作用风险并确保充分给药。随着病毒疗法从实验室走向临床,讨论使这一转变更顺畅的因素很重要。在本文中,我们描述了与溶瘤病毒疗法和脑肿瘤治疗相关的当前临床证据,以及将其纳入神经外科工作流程时需要考虑的因素。