Existe-t-il une place pour la thérapie génique en transplantation d'organes?

Gianello, Pierre [UCL]

The major research objectives in organ transplantation are to palliate the lack of organs, to decrease the adverse effects of chronic immunosuppression and to improve medium-term and long-term graft survival. Xenotransplantation and induction of a permanent and specific tolerance to an allograft therefore represent two main lines of research which could partly resolve the problems of organ transplantation. The objective of this article is to evaluate the possible role of gene therapy in the development of xenotransplantation and induction of allograft tolerance. They review the various gene vectors currently available as well as the routes of administration of these vectors specific to transplantation. The place of gene therapy is then evaluated in the context of allo- and xenotransplantation. In allotransplantation, transfection of certain genes of interest into the transplant organ before implantation or into the recipient's immune system is considered. Transfection into the transplant organ of genes coding for immunomodulating cytokines (TGF-beta, IL-4, IL-10, etc.), molecules which block the second signal (CTLA4-Ig) or molecules responsible for apoptosis (Fas/FasL) is discussed. The value of gene therapy in the recipient's immune system consists of transfection onto the recipient's bone marrow cells of genes coding for major histocompatibility system molecules (HLA-DR, DQ, etc.). In xenotransplantation, gene therapy will certainly play a major role in the development of transgenic pigs expressing, on the surface endothelium of their organs, certain human molecules which regulate the activity of complement (CD55, CD59, etc.) or which modify the expression of glycosylated xenoantigens (alpha-galactosyl) recognized by performed antibodies.