Effective treatment options for peritoneal surface malignancies (PSMs) are scarce. Oncolytic virotherapy with recombinant vaccinia viruses might constitute a novel treatment option for PSM. We aimed to identify the most effective oncolytic vaccinia virus strain in two murine mesothelioma cell lines and the oncolytic potential in a murine model of peritoneal mesothelioma. Cell lines AB12 and AC29 were infected in vitro with vaccinia virus strains Lister (GLV-1h254), Western Reserve (GLV-0b347), and Copenhagen (GLV-4h463). The virus strain GLV-0b347 was shown most effective in vitro and was further investigated by intraperitoneal (i.p.) application to AB12 and AC29 mesothelioma-bearing mice. Feasibility, safety, and effectiveness of virotherapy were assessed by evaluating the peritoneal cancer index (PCI), virus detection in tumor tissues and ascites, virus growth curves, and comparison of overall survival. After i.p. injection of GLV-0b347, virus was detected in both tumor cells and ascites. In comparison to mock-treated mice, overall survival was significantly prolonged, ascites was less frequent and PCI values declined. However, effective treatment was only observed in animals with limited tumor burden at the time point of virus application. Nonetheless, intraperitoneal virotherapy with GLV-0b347 might constitute a novel therapeutic option for the treatment of peritoneal mesothelioma. Additional treatment modifications and combinational regimes will be investigated to further enhance treatment efficacy.
腹膜表面恶性肿瘤(PSMs)的有效治疗选择稀缺。利用重组痘苗病毒的溶瘤病毒疗法可能为PSM提供一种新的治疗选择。本研究旨在确定两种小鼠间皮瘤细胞系中最有效的溶瘤痘苗病毒株,并评估其在腹膜间皮瘤小鼠模型中的溶瘤潜力。在体外,用痘苗病毒株Lister(GLV-1h254)、Western Reserve(GLV-0b347)和Copenhagen(GLV-4h463)感染AB12和AC29细胞系。结果显示,GLV-0b347病毒株在体外最为有效,因此进一步通过腹腔注射给携带AB12和AC29间皮瘤的小鼠进行研究。通过评估腹膜癌指数(PCI)、肿瘤组织和腹水中的病毒检测、病毒生长曲线以及总生存期的比较,评估了病毒疗法的可行性、安全性和有效性。腹腔注射GLV-0b347后,在肿瘤细胞和腹水中均检测到病毒。与模拟治疗的小鼠相比,总生存期显著延长,腹水发生率降低,PCI值下降。然而,仅在病毒应用时肿瘤负荷有限的动物中观察到有效治疗。尽管如此,GLV-0b347的腹腔病毒疗法可能为腹膜间皮瘤的治疗提供一种新的治疗选择。未来将研究进一步的治疗调整和联合方案,以增强治疗效果。