We are focusing on tolerance induction through hematopoietic chimerism and the investigation of costimulation blockade for immunomodulation.
Despite modern immunosuppressive drug therapy long-term graft survival remains limited. The focus of our group is therefore to develop strategies to improve long-term outcome after organ transplantation. The optimization of immunosuppressive drug therapy is our short-term goal and the induction of donor-specific immunological tolerance our long-term vision.
The approach we focus on is to induce 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 particularly robust state of tolerance and has been demonstrated to work not only in rodents, but also in large animals (including non-human primates) and notably in a pilot series of renal transplant recipients in the clinic. However, even though ever milder experimental regimens for the induction of mixed chimerism have been developed, none is ready for widespread clinical translation due to remaining toxicities. Our group is working on the development of refined protocols for the transplantation of allogeneic hematopoietic cells and the delineation of the immunological mechanisms occurring in these models.
Costimulation blockers have a critical role in recently developed experimental tolerance models and the first compounds are entering the clinical setting as immunosuppressants. We are interested in delineating the mechanisms of action of costimulation blockers in both settings with the goal of improving their efficacy.
Our work has been funded through the Austrian Science Fund (FWF) (SFB F2310-B13, DK W1212-B09 , P21989, TRP 151-B19), the ROTRF (CI 110578928) and the industry (Novartis, Bristol-Myers Squibb, Teva).