Grant: Travel Awards - Institute Community Support

Epithelial ovarian cancer (EOC) metastasis involves malignant cells shedding from the primary tumour, accumulation and aggregation into multicellular spheroids in the abdomen, and adhesion of these clusters to the abdominal wall to establish secondary tumours. Like many cancers, EOC tumours exhibit extensive cellular differences between patients and within any given tumour which can hinder effective treatment particularly with new molecularly-targeted therapies. We have performed cross-comparisons of three viruses for their therapeutic potential to treat EOC. A rabbit pox virus, Myxoma virus (MYXV), a construct of vaccinia virus (vvDD), and a relatively new agent, Maraba virus (MRBV). We have determined that several EOC cell lines are efficiently killed by MRBV in our in vitro model of EOC metastasis while MYXV and vvDD viruses infect and kill EOC cells to a much lesser extent than MRBV. In addition, MXYV and vvDD oncolytic potential is almost completely attenuated in EOC spheroids. Interestingly, upon EOC spheroid re-attachment (a model of secondary tumour formation), the oncolytic activity of MYXV and vvDD is restored. Interestingly, our infections of clinical isolates of EOC cells from a single patient received over the course of one year has allowed us to identify a great deal of variability in terms of susceptibility to MRBV over the course of disease. Moreover, our infections of cloned cells expanded from single cells of one of these isolates allowed us to stratify susceptibility to MRBV into two sets: one set that is susceptible to MRBV killing, and the other that exhibits a 1000-fold greater resistance to virus induced cell death. Taken together, this new data is the first to demonstrate the potential for differential efficacy of virus therapy between patients, within a patient over time, and within a single ovarian tumour. We are currently investigating the molecular determinants which define susceptibility to these viral agents.