Redirecting Tregs to the HLA-A2 Antigen for Transplant Tolerance

Abstract

Kidney transplantation is currently the preferred solution for organ replacement in patients with end-stage renal disease (ESRD). While nearly all transplanted grafts will survive in a short-term (up to one year post-transplant) period, graft survival rates decline at a linear rate with increasing time. This is largely contributed by chronic allograft rejection against alloantigens in the transplanted graft. One of the most commonly mismatched alloantigen is HLA-A2. Immunosuppressants have proven to be effective in promoting short-term graft survival, but are ineffective at improving long-term tolerance due to their associated toxicities and adverse events. As such, a novel therapeutic solution is necessary to overcome chronic allograft rejection. This study proposes that chimeric antigen receptor (CAR)-expressing regulatory T-cell (Treg) therapy specific to the HLA-A2 antigen (CAR-A2 Tregs) may be the solution in overcoming the immunological barrier of long-term graft tolerance.