Transplantation Immunology
Despite major advances over the last decades, long-term outcome after organ transplantation remains limited and immune-mediated injury continues to be a leading cause of graft loss.
Our overall aim is to improve long-term outcome after organ transplantation through better control of the immune response towards the graft.
Pre-clinical research
The indispensable lifelong treatment with immunosuppressive drugs is only partially effective in inhibiting chronic graft loss and is accompanied by severe side effects. Therefore, the intentional establishment donor-specific immunological tolerance remains the ultimate goal of transplantation research.
We focus on inducing tolerance through the transplantation of donor hematopoietic stem cells and the establishment of mixed chimerism (i.e. coexistence of donor and recipient hematopoietic cells in the host). This strategy leads to a robust state of transplantation tolerance and has been demonstrated to work not only in rodents, but also in large animals and notably in pilot series of renal transplant recipients in the clinic. However, no protocol is currently ready for widespread clinical translation due to remaining toxicities. A critical step towards the goal of non-toxic protocols is the use of regulatory T cell (Treg) cell therapy as part of chimerism-based tolerance regimens.
A critical step towards the goal of non-toxic protocols is the use of regulatory T cell (Treg) cell therapy as part of chimerism-based tolerance regimens.) To this we have also designed a novel CAR for use in Tregs to modulate the alloresponse.
In our pre-clinical research we use various mouse models, including models of vascularized heart transplantation, regulatory T cell transfer and bone marrow transplantation.
Clinical research
We are currently translating our recently developed pre-clinical Treg-based chimerism treatment protocol to the setting of clinical kidney transplantation. In an ongoing single-center phase I/II trial HLA-mismatched living donor kidney transplant recipients are treated with a combination cell therapy consisting of the administration of polyclonal recipient Tregs and donor bone marrow cells (clinicaltrials.gov NCT03867617).
Research platform transplantation
Transplantation is one of six defined areas of research of the MedUni Vienna. The research platform transplantation (rpt.meduniwien.ac.at), which is co-ordinated by Thomas Wekerle together with Rainer Oberbauer, promotes the research efforts in the field of transplantation at the MedUni Vienna through various activities, including an international seminar series and a start-up grant program.