溶瘤病毒（OV）疗法是治疗中枢神经系统（CNS）内传统治疗难治性癌症（例如胶质母细胞瘤）的有希望的新型治疗方式。尽管OV已获得监管部门批准用于中枢神经系统，但其疗效受到与递送、免疫反应不足/过度活跃以及大多数中枢神经系统恶性肿瘤的“免疫冷”性质相关的障碍的阻碍。 SUMO（小泛素样修饰剂）是一个蛋白质家族，可作为多种关键生理过程（包括宿主免疫反应）的高级调节剂。 SUMO 途径也与野生型病毒和中枢神经系统恶性肿瘤的发病机制有关。因此，OV 生物学与 SUMO 途径的交叉使得 SUMOtherapeutics 作为单独或与其他免疫治疗剂协同增强 OV 疗效的辅助疗法特别有趣。因此，作者在此提供：1）SUMO 通路及其在中枢神经系统恶性肿瘤中的作用的概述； 2）描述CNS靶向OV的当前状态； 3) 描述 SUMO 途径与病毒生命周期和宿主免疫反应之间的相互作用。版权所有 © 2023 Karandikar, Suh, Gerstl, Blitz, Qu, Won, Gessler, Arnaout, Smith, Peruzzi, Yang, Fr​​iedman 和 Bernstock。

Oncolytic viral (OV) therapies are promising novel treatment modalities for cancers refractory to conventional treatment, such as glioblastoma, within the central nervous system (CNS). Although OVs have received regulatory approval for use in the CNS, efficacy is hampered by obstacles related to delivery, under-/over-active immune responses, and the "immune-cold" nature of most CNS malignancies. SUMO, the Small Ubiquitin-like Modifier, is a family of proteins that serve as a high-level regulator of a large variety of key physiologic processes including the host immune response. The SUMO pathway has also been implicated in the pathogenesis of both wild-type viruses and CNS malignancies. As such, the intersection of OV biology with the SUMO pathway makes SUMOtherapeutics particularly interesting as adjuvant therapies for the enhancement of OV efficacy alone and in concert with other immunotherapeutic agents. Accordingly, the authors herein provide: 1) an overview of the SUMO pathway and its role in CNS malignancies; 2) describe the current state of CNS-targeted OVs; and 3) describe the interplay between the SUMO pathway and the viral lifecycle and host immune response.Copyright © 2023 Karandikar, Suh, Gerstl, Blitz, Qu, Won, Gessler, Arnaout, Smith, Peruzzi, Yang, Friedman and Bernstock.