Clinical trials for induction of renal allograft tolerance.

Abstract

This review summarizes the current state of clinical trials for tolerance induction of human leukocyte antigen-matched or mismatched renal allografts via peritransplant infusion of donor bone marrow-derived products. Recent efforts to apply infusion of expanded regulatory T-cell preparations to minimize immunosuppressive dosages are also reviewed. Three centers in the United States have reported clinical trials for tolerance induction in recipients of living donor kidney transplants via donor hematopoietic stem cell transplantation. They have observed varying degrees of successful renal allograft tolerance induction following the establishment of either transient or persistent donor chimerism.A more recent clinical trial planned to evaluate administration of regulatory T cells to harness the immune response has recently been initiated in eight centers in Europe and the United States. Tolerance induction in clinical kidney transplantation from live donors has been achieved by donor hematopoietic stem cell transplantation. Improving the consistency and safety of tolerance induction and extending successful protocols to other organs, as well as to organs from deceased donors, are critical next steps to bringing tolerance to a wider range of clinical applications.