Allograft Rejection: Acute and Chronic Studies

Organ transplantation represents the only possible therapeutic intervention for a large number of end-stage renal diseases. The current immunosuppressive drugs are very efficient to overcome the acute rejection; however, their continuous administration exposes patients to a great risk of developing opportunistic infections and cancer. The typical drug cocktail consisting of a high-dose steroid, a calcineurin inhibitor and an anti-metabolite is effective but any of these drugs exert specific side effects including nephrotoxicity in the long-term. The rate of late graft loss, essentially due to the onset of chronic allograft nephropathy, is still too excessive and can be predicted by a previous episode of acute rejection. Attempts to limit the early insults damaging the graft should exert beneficial effects on long-term graft functionality. Gene therapy, originally conceived to cure genetic diseases, has been successfully applied in the last decade to organ transplantation with the final aim to overcome acute or chronic rejection. Transfer of genes that encode proteins with immunomodulatory properties might represent a therapeutic tool to reduce and hopefully avoid the long-life administration of drugs. In this chapter, we review gene therapy studies carried out in the context of experimental organ/tissue allotransplantation to overcome acute and chronic graft rejection.