Grant: Team Gr.: Interv. Trial in Inflam. for Chronic Cond. - Res. Teams Gr. - General

A process called immune tolerance allows our immune system to fend off dangerous foreign substances yet leave our own tissues untouched. When immune tolerance fails, it results in chronic inflammation, leading to many different diseases, including cardiovascular and autoimmune diseases. It can also lead to transplant rejection. As there are no medications to promote immune tolerance, patients with chronic inflammatory diseases are often on long-term immune suppressants that are not curative and have toxic side-effects. Our goal is to move beyond symptom management for inflammatory disease and find safe, long-term solutions. We have been working towards this goal by developing a therapy that takes advantage of a specialized type of white blood cell, called regulatory T cells, or Tregs, which suppress undesired immune responses, promote tissue healing and help re-establish a balanced immune system. Tregs are rare in circulating blood, but we have shown that an organ called the thymus (which is routinely removed and discarded during heart surgery) is an abundant source of easily-isolated and pure Tregs. In the last decade of research, we developed methods to isolate thymus Tregs and grow large numbers of them for clinical use, and also showed that thymus Tregs improve immune tolerance in mouse models of transplantation. We now aim to conduct a clinical trial in humans to determine if thymus Tregs are a safe and effective way to prevent chronic inflammation after bone marrow (immune system) transplantation, when the donor immune system has the potential to attack healthy tissue in the recipient. We have partnered with a cross-Canada team of clinicians, national medical networks and people with lived experience to design and conduct this clinical trial. Once we establish safety and effectiveness of thymic Tregs in the context of transplantation, we will be able to extend testing of this "off-the-shelf" Treg therapy to many other inflammatory diseases.