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

Blood and bone marrow transplants can be used to treat blood cancers such as leukemia. The transplant can provide a cure when the donor immune cells attack and kill leukemia cells. Unfortunately, the donor cells often also attack the patient's own tissue, causing serious short- and long-term consequences. To prevent these negative immune responses without inhibiting the anti-cancer effect of the transplant, our strategy is to also give patients a dose of the type of immune cell that suppress the negative immune responses. These are called regulatory T cells, or Tregs. Initial studies with Tregs have been promising, but there are many challenges to using Tregs as a therapy. One major issue is that Tregs are very rare - less than 1% of white blood cells - so to obtain enough cells to use in a patient, we must develop methods to isolate and grow Tregs. Rather than obtaining rare Tregs from blood, my goal is to isolate these cells from Treg-rich tissue and increase their numbers in the lab. For this study, the tissue source is the thymus gland, an immune organ located above the heart that is routinely removed during pediatric cardiac surgery. The thymus is a plentiful source of Tregs that are more uniform in their characteristics than Tregs in the blood. I am developing a protocol to grow thymus-derived Tregs that is compatible with clinical standards and will also identify new conditions that can further enhance Treg growth in culture. Ultimately, this work will result in methods to efficiently produce Tregs for cell therapy applications, a crucial step towards the clinical use of thymus-derived Tregs as a therapy to improve transplantation outcomes.