Grant: Project Grant

Transplantation is the best treatment for end-stage organ failure. In the past ten years, more than 20,000 Canadians have had their lives improved or saved by donated organs. Organ transplantation is only possible because immunosuppressive drugs prevent rejection, but these drugs also bring increased risks of infection, cancer, and many other side effects. Our goal is to find ways to educate the patient's immune system to accept a transplanted organ, without high doses of immunosuppressive medication. Our strategy is to harness the natural properties of a type of white blood cell called a T regulatory cell (Treg). Tregs modulate immune responses -not too much, not too little - and if used therapeutically, they could control immune responses to transplanted tissues and organs. Here, we aim to discover ways to engineer Tregs so that they are maximally effective. First we will modify Tregs so they can be specifically activated by the foreign tissue of the transplant. We will test the therapeutic effect of these genetically-modified Tregs in animal models of transplantation (specifically, transplant of pancreas cells or lung) and explore the possible safety-related limitations of the approach. We will also ask if genetically-modified Tregs have the potential to induce long-lasting effects, meaning that "booster" injections of more Tregs may not be needed to control immune responses. Finally, we will create new ways to manufacture Tregs using conditions to tailor their function depending on the clinical context. These tailored Tregs will be evaluated in animal models to test their effect. Data generated in this project will help in the design and testing of Tregs as a cell therapy in transplantation. By creating new ways to minimize the reliance on immunosuppressive drugs, our research has the potential to significantly increase the long-term success of transplantation.