Grant: KRESCENT / CIHR Fellowship

Transplantation is the best and sometimes only treatment for end-stage organ failure. In the last ten years, the lives of more than 20,000 Canadians have been improved, extended, or saved by donated organs. lmmunosuppressive drugs make transplantation possible, but since these drugs cannot suppress just the cells reactive to the transplanted organ but suppress the entire immune system, these drugs come at the price of an increase in infection and cancer risk. The drugs are also not perfect; many organs are still lost to rejection. Our goal is to improve the success of transplantation, by finding ways to re-educate the recipient's immune system to tolerate the transplanted organ. Our strategy is to harness the natural immunosuppressive properties of a type of white blood cell called T regulatory cells (Tregs). Tregs naturally regulate immune responses by ensuring the immune system attacks infectious or harmful substances without over-reacting to self or non-harmful foreign proteins. In the last 10 years, research has shown that Tregs could be used as a cell-based therapy to induce immune tolerance and prevent organ rejection. The efficacy of Treg cell therapies can be significantly enhanced if the cellular product is enriched for Tregs that recognize an target that is specific to the transplanted organ. Dr Levings' lab developed a method to improve the potency of Tregs by engineering them to express a protein that activates them when they are in the presence of a transplant. My goal is thus to study the potential of those engineered Tregs to control allograft rejection and lower the chances that transplant recipients will reject the donor organ.