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

A hallmark of cancer is the accumulation of DNA mutations that allow cancer cells to grow and multiply. Recent technological advances in genetic sequencing have dramatically lowered the cost of identifying these mutations so we can now identify all mutations in a patient's tumour. Studies to date indicate that human tumours contain tens to thousands of mutations, the vast majority of which are unique to individual patients. The next major challenge is to develop clinically feasible, cost-effective strategies to therapeutically target the complex mutational landscape of human cancer. The immune system recognizes and destroys cells that are abnormal due to infection or mutation. However, in the case of cancer, the immune system seems to ignore many mutations with the result that tumours are able to grow. I hypothesize we can use vaccines to fully activate the immune system to recognize mutations and destroy tumours. To test this idea, we used next generation sequencing to identify mutations present in an experimental set of five different mouse breast tumours. After we validate the mutations, we will develop vaccines made of small segments of proteins that mimic the mutations. To test whether these vaccines can induce a therapeutic effect, we will implant tumour cells containing the relevant mutations into mice. Once tumours are well established, we will vaccinate mice and measure the level of immune system activation. We expect vaccination to elicit a potent immune response that leads to tumour regression. If successful, this project will pave the road to the use of personalized vaccines to treat cancer. As the cost of sequencing an entire human genome approaches the $1000 mark, it will become feasible to routinely subject patients' tumours to genomic sequencing. The mutations identified by sequencing could then be used to design personalized vaccines that trigger the patient's immune system to recognize and destroy cancer cells throughout the body.