Department of Gene Therapy, Sirius University of Science and Technology, 354340 Sochi, Russia.
Front Biosci (Landmark Ed). 2024 Oct 31;29(11):374. doi: 10.31083/j.fbl2911374.
Oncolytic viruses (OVs) represent a targeted anti-cancer therapy approach due to their ability not only to selectively infect and destroy malignant cells but also to induce an immune response. Vesicular stomatitis virus (VSV) offers a promising platform due to its low prevalence and pathogenicity in humans, lack of pre-existing immunity, easily manipulated genome, rapid growth to high titers in a broad range of cell lines, and inability to integrate into the host genome. However, despite its many advantages, many unresolved problems remain: problematic production based on the reverse genetics system, oncological selectivity, and the overall effectiveness of VSV monotherapy. This review will discuss various attempts at viral genome modifications aimed at improving the oncolytic properties of VSV. These strategies include inhibition of viral genes, modification of genes responsible for targeting cancer cells over healthy ones, insertion of foreign genes for boosting immune response, and changing the order of viral and inserted foreign genes. In addition, possible ways to improve VSV-based anti-tumor therapy and achieve higher efficiency will be considered by evaluating the effectiveness of various delivery methods as well as discussing treatment options by combining VSV with other groups of anticancer drugs.
溶瘤病毒(OVs)因其不仅能够选择性地感染和破坏恶性细胞,还能诱导免疫反应的能力,代表了一种靶向抗癌治疗方法。由于水疱性口炎病毒(VSV)在人类中发病率和致病性低、缺乏预先存在的免疫、易于操纵基因组、在广泛的细胞系中快速生长到高滴度以及不能整合到宿主基因组中,因此它提供了一个有前途的平台。然而,尽管有许多优点,但仍存在许多悬而未决的问题:基于反向遗传学系统的生产问题、肿瘤选择性以及 VSV 单药治疗的整体效果。本综述将讨论旨在提高 VSV 溶瘤特性的各种病毒基因组修饰尝试。这些策略包括抑制病毒基因、修饰负责靶向癌细胞而不是健康细胞的基因、插入增强免疫反应的外源基因以及改变病毒和插入外源基因的顺序。此外,还将通过评估各种递药方法的有效性以及通过将 VSV 与其他组抗癌药物联合治疗来探讨治疗选择,来考虑改善基于 VSV 的抗肿瘤治疗和提高效率的可能方法。