Efficacy of Different Oncolytic Vaccinia Virus Strains for the Treatment of Murine Peritoneal Mesothelioma

Simple Summary Effective treatment options for malignant diseases affecting the peritoneum, the inner surface of the abdominal cavity and organs, are scarce. Oncolytic virotherapy uses self-replicating viruses that target malignant cells and kill them selectively. In our work, we investigated the ability and potential of modified vaccinia viruses to infect and kill peritoneal mesothelioma cells in a mouse model. Among others, Western Reserve strain of vaccinia viruses (GLV-0b347) resulted most effective for the treatment of mouse mesothelioma. In mice diseased with mesothelioma, tumor mass and complications could be reduced and survival was prolonged when treated with vaccinia virus compared to untreated animals. Taken together, this new treatment approach showed promising results in a mouse peritoneal cancer model. Future research will focus on further improvement of this therapy.Abstract 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.