Yurttas Can, Beil Julia, Berchtold Susanne, Smirnow Irina, Kloker Linus D, Sipos Bence, Löffler Markus W, Königsrainer Alfred, Mihaljevic André L, Lauer Ulrich M, Thiel Karolin
Department of General, Visceral and Transplant Surgery, University Hospital of Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany.
Virotherapy Center Tübingen (VCT), Department of Medical Oncology and Pneumology, University Hospital of Tübingen, Otfried-Müller-Str. 10, 72076 Tübingen, Germany.
Cancers (Basel). 2024 Jan 15;16(2):368. doi: 10.3390/cancers16020368.
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(PSM)的有效治疗方案匮乏。重组痘苗病毒溶瘤病毒疗法可能成为PSM的一种新治疗选择。我们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,以及在小鼠腹膜间皮瘤模型中的溶瘤潜力。在体外,用痘苗病毒株李斯特(GLV-1h254)、西储(GLV-0b347)和哥本哈根(GLV-4h463)感染细胞系AB12和AC29。病毒株GLV-0b347在体外显示出最有效,并通过腹腔内(i.p.)注射到携带AB12和AC29间皮瘤的小鼠中进行进一步研究。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比较,来评估病毒疗法的可行性、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,总生存显著延长,腹水出现频率降低,PCI值下降。然而,仅在病毒应用时间点肿瘤负荷有限的动物中观察到有效治疗。尽管如此,腹腔内用GLV-0b347进行病毒疗法可能成为治疗腹膜间皮瘤的一种新治疗选择。将研究额外的治疗改进措施和联合治疗方案,以进一步提高治疗效果。