Stem cells engineered to express self-antigen to treat autoimmunity

Abstract

Autoimmune diseases are incurable. We propose a combination curative strategy using haematopoietic stem cells and gene therapy. The strategy should establish molecular chimerism with culprit antigen expressed by donor antigen-presenting cells in the thymus, resulting in immunological tolerance. Our strategy is based on the intrathymic tolerance and disease resistance established by transgenic expression of antigen in the thymus under control of an MHC class II promoter. We propose that transplantation with genetically engineered stem cells provides an advance over current autologous bone marrow transplantation, in that it should remove the significant risk of disease relapse.