Project 467024

Oncolytic virotherapy is a form of cancer therapy that utilizes oncolytic viruses (OVs) to preferentially infect and kill tumour cells. We have previously demonstrated that some OVs in clinical trials likely lack efficacy due to the off-target infection of activated T cells when used in multi-dosing protocols. An increase in oxidative stress due to the increase in reactive oxygen species (ROS) during viral replication may contribute to multiple aspects of viral pathogenesis. This project looks at the ability of some antioxidants, compounds that inhibit oxidation and protect cells from ROS-mediated damage, to prevent off-target infection of activated CD4+ and CD8+ T cells. If antioxidants can prevent off-target viral infection of T cells, co-administering antioxidants during a rapid multi-dosing protocol with OVs has the potential to increase their efficacy. Thus far, the antioxidants N-acetyl L cysteine and catalase have proven promising candidates for improving cancer immunotherapies by preventing T cell of target infection with vesicular stomatitis virus. This project will be extended to a murine melanoma survival model to better determine which combination therapies extend survival.