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DOI: 10.1055/s-0031-1295991
Novel treatment approach for therapy of peritoneal carcinosis using Vaccinia virotherapeutics
Introduction: No standard curative therapy is available for peritoneal carcinosis often caused by gastrointestinal, but also by hepatobiliary tumors. A novel strategy to kill the cancer cells within the peritoneal cavity could be the use of virotherapeutics combined with the surgical method of peritonectomy. JX–594, an oncolytic poxvirus, already demonstrated antitumoral activities in patients with primary or metastatic liver cancer. The oncolytic Vaccinia virus GLV–1h68 already revealed its ability to reduce the cell mass of solid tumors of several cancer species in human xenograft models and is currently tested in clinical trials. This vector GLV–1h68, encoding marker genes like green fluorescent protein (GFP) and β-galactosidase (β-gal) seems to be a useful tool in the fight against gastrointestinal/hepatobiliary tumors and peritoneal carcinosis. Aims: GLV–1h68 should be tested with regard to its ability to infect, to replicate in and to lyse tumor cell lines of different origin in vitro. Methods: Infection of cancer cells was monitored using GFP and β-gal-expression. Replication behaviour of GLV–1h68 was investigated in a standard plaque assay resulting in viral growth curves. A viability assay and a lactatdehydrogenase (LDH) release assay were used to determine the cytotoxic effects of GLV–1h68. Results: GLV–1h68 was able to infect all tested cell lines even at a multiplicitiy of infection of 0.1. Growth curves revealed massive viral replication and ended up in increased viral titres. Cell cytotoxicity assays showed significant cell mass reduction and increased LDH-release which could be attributed to the cytotoxic effects of GLV–1h68. Conclusion: GLV–1h68 effectively infected, replicated in and killed all tumor cell lines being evaluated in this study. This virotherapeutic probably will provide a more efficient treatment of patients suffering from peritoneal carcinosis. A first phase I/II clinical trial currently is operational at University Clinic Tübingen.
Peritoneal carcinosis caused by gastrointestinal/hepatobiliary tumors - Virotherapy