Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Malignant melanoma (MM) is the most aggressive form of skin cancer. MM accounts for almost 5% of new cancer cases every year, a number that is increasing in countries such as Canada with predominately fair-skinned individuals. A significant percentage of MM cases continue to be fatal, an unfortunate reality due to the aggressive nature of MM and the inadequacy of conventional therapies. Oncolytic viruses (OVs) are viruses that are able to target and destroy cancer cells and nearby tumour-supporting cells while leaving normal cells unaffected. Despite past successes using OVs, MM remains deadly and better medical tools are needed to fight aggressive tumours. We have identified an engineered virus, Maraba-MG1, which has increased cancer-killing properties when compared to preceding OVs that have previously shown success in clinical trials. In addition, we have developed a screening approach using another virus, Sindbis, which is capable of over-expressing artificial micro RNAs (amiRNAs), allowing us to select for ways to more specifically target MM cells while leaving normal cells untouched. Due to convincing preliminary work, we believe that we can create a far superior OV to target MM by combining the newly engineered and more potent OV with the amiRNA-screening approach mentioned above. This project has four specific aims: (1) identifying amiRNAs that will allow the most specific targeting of cancer cells, (2) engineering the most efficient sequences into Maraba-MG1 and testing for growth, (3) assessing safety and efficacy of the newly-engineered viruses in MM tissue explants, and (4) identifying cellular targets of the newly-engineered viruses. Upon successful completion, we will have engineered better cancer-killing clinical tools to target MM than have previously existed, and developed a better understanding of the biology of MM. This work has the potential to have a significant impact on MM patients in Canada and around the world.