Z Gastroenterol 2011; 49 - P173
DOI: 10.1055/s-0031-1285445

Novel treatment approach of peritoneal carcinosis using Vaccinia virotherapeutics

N Mayer 1, M Zimmermann 1, S Berchtold 1, A Königsrainer 2, J Glatzle 2, I Königsrainer 2, M Bitzer 1, UM Lauer 1
  • 1Medical University Hospital Tübingen, Department of Internal Medicine I, Tübingen, Germany
  • 2University Hospital, Department of General, Visceral and Transplant Surgery, Tübingen, Germany

Introduction: Two of the most frequent cancer species worldwide are colorectal and ovarian cancer often spreading into the peritoneal cavity. So far, there is no standard curative therapy available for peritoneal carcinosis. A novel strategy to kill all cancer cells within the peritoneal cavity could be the use of a virotherapeutic combined with the surgical method of peritonectomy. JX-594, an oncolytic poxvirus, already has demonstrated antitumoral activities in patients with primary or metastatic liver cancer. Furthermore, 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 phase I clinical trials. This vector GLV-1h68, encoding marker genes like green fluorescent protein (GFP) and β-galactosidase seems to be a useful tool in the fight against gastrointestinal tumors and peritoneal carcinosis.

Aims: The well characterized attenuated oncolytic virus GLV-1h68 should be tested with regard to its ability to infect, to replicate in and to lyse tumor cell lines of gastrointestinal and gynaecological origin in vitro.

Methods: Three colorectal and ovarian cancer cell lines were applied for our in vitro studies. Infections were monitored using the vector-encoded GFP and the β-galactosidase-expression. Furthermore, the 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 effect.

Results: GLV-1h68 was able to infect all tested cell lines even at multiplicities of infection (MOI) as low as 0.1. The results of the growth curves revealed massive viral replication in tumor cells and ended up in increased viral titres in cell lysates 96 hours post infection. Cell cytotoxicity assays showed significant cell mass reduction and increased LDH-release which could be attributed to the efficient cytotoxic effects of GLV-1h68.

Conclusion: GLV-1h68 effectively infected, replicated in and killed all cell lines of gastrointestinal and gynaecological origin. This virotherapeutic probably will provide a more efficient treatment of patients suffering from peritoneal carcinosis.