Research Group

  • Dr David Mathes, Principal Investigator
  • Dr Rainer Storb, Res. Associate
  • Dr Scott Graves, Res. Associate
  • Dr Tiffany Miwongtum, Technician

Location

  • Fred Hutchinson Cancer Research Center, Seattle, USA

Title

  • Immune Tolerance to Face and Hand via Mixed Chimerism

The era of clinical human composite tissue transplantations has been established by the successful transplantation of the hand, larynx, abdominal wall, and face. The clinical application of composite tissue allografts (CTA) allows for the reconstruction of what was previously un-reconstructable. However, all of these transplants are currently dependent on chronic immunosuppression for their survival. The daily use of immunosuppression has the potential to cause serious, even fatal, side effects. More importantly however, all of these transplants have demonstrated episodes of rejection that required treatment with additional steroids, the use of monoclonal antibodies or an increase in the overall level of immunosuppression. Immunologic tolerance would allow for the long-term survival of these organs without the need for chronic immunosuppression. This would significantly impact the risk-benefit ratio and allow for the more widespread use of CTA in the reconstruction of lost limbs and severe facial deformities.

While tolerance to the skin has been achieved in certain small animal models, it has remained elusive in large animal models. We have developed a pre-clinical large animal model to study tolerance protocols for use in composite tissue transplantations. The goal of our research program is to develop methods for inducing donor-specific tolerance of composite tissue transplants through the establishment of mixed chimerism. We propose to use our pre-clinical canine model to induce tolerance to composite tissue allografts through the induction of mixed chimerism via a hematopoietic stem cell transplant with a minimal conditioning regimen. The further refinement of this protocol will lead to the establishment of a clinical protocol that can be used in human composite tissue transplantation.

Final Report