Grant: Doctoral: Vanier Canada Graduate Scholarships

The immune system is designed to recognize and kill cancer cells. Therefore, cancers have had to develop strategies to evade a patient's immune system. Biotherapies represent a safe and effective new strategy to treat cancers by manipulating natural biological systems to enhance tumour-specific immune responses. It is now known that cancers can die in one of two ways: immunogenic or non-immunogenic cell death. Immunogenic cell death (ICD) induces cancer-specific immune responses that can kill tumour cells anywhere in the body. Oncolytic viruses (OVs) represent a particularly promising type of biotherapy. These are naturally occurring viruses that do not cause disease. They take advantage of the fact that most cancers shut down antiviral mechanisms as part of the process of evading cell death. OVs typically cause no harm to normal cells but can infect and kill cancerous cells throughout the body. The ability of OVs to cause ICD is highly variable and there is much room for improvement. Therefore, we propose to enhance ICD by combining OVs with photodynamic therapy (PDT). Specifically, PDT uses a light-sensitive drug that concentrates inside a tumour. An external light source can then be safely applied to the cancer site to activate the drug, which then kills the local cancer cells. PDT can only be applied to superficial cancers, such as skin cancers, but since it causes ICD, the ensuing immune response can target cancer cells anywhere in the body. Traditionally, PDT was limited to treating tumours within millimeters of the surface of the skin. We propose to use cutting-edge technology to penetrate up to several centimeters depth, allowing cancers such as breast tumours to be treated. We hypothesize that OVs and PDT will be complementary, resulting in potent immune responses that can kill cancer cells anywhere in the body that escape the initial direct effects of each monotherapy. Our initial targets of this therapy will be melanomas in the brain and breast cancers.