Mari Lowe Center for Comparative Oncology Research

3800 Spruce Street, Philadelphia, PA 19104

Investigation of canine regulatory T cell biology and its implications for cancer immunotherapy and transplantation tolerance

The presence of regulatory or suppressor T cells are a significant barrier to the success of immunotherapeutic approaches to treat cancer in humans. However, the significance of these cells and the role that they play in canine cancers has yet to be formally demonstrated. Researchers in Dr. Mason’s laboratory at PennVet are seeking to characterize the biology of canine regulatory T cells and to understand how they may be manipulated for therapeutic purposes. While the potent immunosuppressive function of these cells is detrimental to cancer immunotherapy, it may be beneficially employed for the treatment of autoimmune disease and strategies to prevent organ rejection after transplantation. Dr. Mason’s group have identified a subset of canine peripheral CD4+ T cells that have the phenotypic characteristics of natural regulatory T cells including surface expression of the IL-2 receptor and intracellular expression of the transcription factor, FoxP3. The low frequency of circulating naturally occurring regulatory T cells indicates that ex vivo activation and expansion of these cells will be required to generate sufficient numbers for immunosuppressive therapies required for autoimmunity and prevention of organ transplant rejection. In the laboratory, we have generated a system that allows for polyclonal expansion of canine regulatory T cells that are capable of suppressing autologous T cell proliferation. It is the overall hypothesis of this project that regulatory T cells isolated and expanded from patients undergoing organ transplant can be used to suppress allo-reactive donor T cells and induce tolerance to the donor graft. Further studies are required to elucidate the mechanisms responsible for canine regulatory T cell mediated suppression prior to the therapeutic use of these cells in phase I clinical trials to prevent organ rejection in transplantation medicine and suppress aberrant immune responses in autoimmune disease.