While transplantation saves lives, patients living with a transplant keep the possibility of rejecting their donated graft very close to their minds. Although long-term survival and quality of life for transplant recipients have steadily increased, too many patients will be relisted for a second or even third transplant over the course of their lives. In addition, the immunosuppressive medications that put graft rejection at bay suppress all immune responses, putting transplant recipients at increased risk of infections and cancer. To help make immunosuppressive medication more specific, immunologists and transplant researchers across Canada are working together to harness the tools buried deep within our own immune system to prevent transplant rejection.

T cell therapy

Researchers have long searched for ways to boost the immune system’s ability to fight off infections, battle cancer, or dampen responses that cause autoimmune diseases. Promising discoveries have directed researchers to study a type of white blood cell called “T regulatory cells” or Tregs, which coordinate immune responses and maintain immune tolerance in the body. In the transplant setting, we believe there is potential to use Tregs as a cell therapy to control the body’s own immune responses without altering healthy immune balance. Tregs can be used to block the response of the recipient’s immune system to signals from the transplanted organ graft which ultimately cause rejection.

There are challenges for bringing a Treg-based therapy into reality: one, designing Tregs that are only active in the presence of a transplant; and two, finding an abundant and stable source of clinical Tregs. Both of these challenges are the focus of intense investigation with teams of Canadian National Transplant Research Program investigators across the country — bringing in cell-manufacturing expertise, chemists, computer programmers, industry partners, and international collaborators. We believe that Treg-based therapies are the future for improving transplant tolerance by building a healthy immune system that strikes a balance between attacking infectious or dangerous substances while not reacting to the recipient’s new organs, cells, and/or tissues.

With over 300 scientists, clinicians, patients, trainees, and collaborators working on seven major projects across Canada, the Canadian National Transplant Research Program (CNTRP) is a multidisciplinary program that aims to increase organ and tissue donation, and to improve the quality of life for transplant recipients. Though the national program’s goals are ambitious, effective teamwork and collaboration have so far yielded excellent results.