Tempering Allorecognition to Induce Transplant Tolerance With Chemically Modified Apoptotic Donor Cells
The development of organ transplantation as a therapy for end stage organ failure is among the most significant achievements of 20th century medicine, but chronic rejection remains a barrier to achieving long term success. Current therapeutic regimens consist of immunosuppressive drugs that are efficient at delaying rejection but are associated with significant risks such as opportunistic infections, toxicity, and malignancy. Thus, the induction of specific immune tolerance to transplant antigens is the coveted aim of researchers. The use of 1 ethyl 3 (3 dimethylaminopropyl)carbodiimide (ECDI) treated, autoantigen coupled syngeneic leukocytes has been developed as a specific immunotherapy in preclinical models of autoimmunity and is currently in a phase II clinical trial for the treatment of multiple sclerosis. In this review, we discuss the use of allogeneic ECDI treated apoptotic donor leukocytes (allo ECDI SP) as a strategy for inducing antigen specific tolerance in allogeneic transplantation. Allo ECDI SP therapy induces long term systemic immune tolerance to transplant antigens by subverting alloimmune recognition and exploiting apoptotic cell uptake pathways to recapitulate innate mechanisms of peripheral tolerance. Lastly, we discuss potential indications and challenges for transitioning allo ECDI SP therapy into clinical practice.
American journal of transplantation official journal of the American Society of Transplantation and the American Society of Transplant Surgeons