Minimization of Immunosuppression and Tolerance Induction in Reconstructive Transplantation

Abstract

Vascularized composite allotransplantation (VCA) is an innovative reconstructive modality for patients sustaining complex injuries not amenable to conventional treatment. Advances in immunosuppression have made VCA a clinical reality and a valid reconstructive option for such patients. The requirement, however, for multi-drug high-dose immunosuppressive regimens with their numerous side effects has hindered widespread clinical application of VCA. There is thus a need for novel immunologic modalities to minimize or even obviate the need for immunosuppression (tolerance induction) while still preserving the allograft and preventing rejection. Recent advances in targeted immunotherapy and cell-based protocols were able to achieve tolerance in selected cases of solid organ transplantation. This paved the way for innovative immunomodulatory protocols now also applied to VCA that aim for minimal immunosuppression or for induction of donor-specific tolerance. These concepts and novel protocols will be discussed in this review.