Characterizing the mechanisms by which oncolytic viruses induce antitumour immunity

Immunotherapy has revolutionized cancer care, in some cases generating cures in patients that have failed all other treatments. Our lab studies a new and exciting form of immunotherapy called oncolytic viruses (OVs). These are viruses that were originally designed to seek out and kill cancer cells in a patient while leaving normal cells unharmed. However, it's now become clear that these viruses work primarily by stimulating the patient's own immune system to fight his or her cancer. How this occurs is not well understood. Currently, the belief in the field is that OVs must first infect the patient's cancer cells to generate an immune response against the tumour. However, my research suggests a very different mechanism. I have found that in many cancer models, OVs can stimulate the immune system to eliminate tumours without first infecting cancer cells. Instead, the OVs infect immune cells in other organs such as the spleen and lymph nodes. These unexpected findings have prompted me to hypothesize that infection of immune cells is what causes tumour regression, and that cancer cell infection is not required. To test this hypothesis, I will do two things. First, I will engineer cancer cells to be resistant to infection by OVs. I will then treat mice bearing these "infection-resistant" tumours with OVs, to determine whether cancer cell infection is required for OV therapy to work. Second, I will identify which immune cells are infected by these viruses, and determine how these infections promote tumour regression. This research will greatly expand our understanding of how OVs work to promote cancer regression. Further, knowledge gained from these studies will allow for the development of new OVs that are better able to stimulate immune responses against tumours. Ultimately, this may result in improved outcomes for patients receiving OV therapy for the treatment of their cancer.