High Dose Post-Transplantation Cyclophosphamide to Induce Delayed Immune Tolerance After Reconstructive Transplantation

ABSTRACT

Developing novel treatment concepts to minimize/avoid immunosuppression by induction of immune tolerance represents the prime task in the field of transplantation. Immunosuppression-free allograft survival has been achieved in several small and large animal models as well as in humans in living-related combined kidney and donor bone marrow transplantation via transient or stable mixed hematopoietic chimerism. This is a concept of particular interest in VCA, as component grafts may inherently contain vascularized donor bone marrow and thus a vital bone marrow niche home to donor-derived hematopoietic progenitor cells. However, as living-related transplantation is ethically precluded in VCA, reconstructive transplantation is limited to cadaveric donors and thus extensive pre-transplant preconditioning is not feasible. Recently, we were able to demonstrate immune tolerance in mice using a peri-transplant induction regimen based on high-dose post-transplantation cyclophosphamide treatment (PT/Cy). In the underlying novel approach, we aim to apply the PT/Cy treatment protocol after the use of conventional immunosuppression to induced a state of delayed tolerance in an attempt to bypass limitation of cadaveric donor settings in VCA.