Extracorporeal Photopheresis (ECP) as a Novel Strategy for Transplant Tolerance Induction

Liver transplantation is a potentially life-saving procedure in people with liver disease that cannot be cured; approximately 6,000 are performed in the United States per year. Despite advances in the field of solid organ transplantation, patients continue to suffer organ rejection and fatal complications secondary to the intense use of immunosuppression (IS) required to prevent rejection. More effective and less toxic treatments are needed for these potentially life-saving transplants to succeed. Induction of donor specific tolerance would allow minimizing the use of IS as well as long-term transplant survival. Extracorporeal photopheresis (ECP) is an FDA approved immune therapy for the treatment of cutaneous T-cell lymphoma. Recently, ECP has been shown to be effective for treating graft-versus-host disease following bone marrow transplant, and rejection following solid organ transplantation. However, the role of ECP in tolerance induction has not been determined. In prior experiments utilizing rodent models of heart and liver transplants, we have demonstrated a significant prolongation of graft survival with a single infusion of photopheresis-treated immune cells. The application of our system to experiments utilizing liver transplants in rats will translate directly into feasible clinical trials in which patients may benefit from significant reduction in immune suppression