Grant: Doctoral Research Award: Priority Announcement - Infection and Immunity

We are studying a breast cancer treatment strategy using viruses modified to selectively kill tumours. These oncolytic ("cancer lysing") viruses both directly kill tumours and also educate the immune system to target cancer cells, helping to prevent tumour recurrence. We have modified vaccinia virus to preferentially grow in cancer cells, killing them, while leaving healthy tissues intact. In breast cancer models, our virus slows tumour growth and extends survival, however, mice still eventually succumb to disease. We aim to increase the effectiveness of virus treatment by combining it with radiation therapy (RT). RT is often used to treat solid tumours such as breast cancer. For patient treatment, sophisticated machinery exists to precisely target RT to tumours and reduce damage to adjacent tissue. One drawback is that cells at the tumour margins, or cells that have spread to distant sites (metastatic cells), evade RT, leading to the return of the cancer. We anticipate that combining RT with an oncolytic virus will allow us to achieve better control of breast cancer in mouse models. To study this, we have access to a specialized image-guided RT machine, the only one of its kind in Western Canada, which allows us to deliver RT to mice with similar precision to that used in humans. We anticipate that RT will clear the bulk of the tumour, while our virus will infect and kill any remaining cancerous cells at the tumour margins, or which have spread to other sites in the body. We also expect that when our virus is combined with radiation it will improve stimulation of the immune system to target the cancer. In this way, the virus will function as a cancer vaccine and prevent metastasis and recurrence. We anticipate that this targeted approach will offer a more effective way of treating breast cancer, while also causing fewer side effects compared to traditional approaches. This will improve the quality of life and long-term outcomes for cancer patients in Canada.