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The blockade of T-cell co-stimulation as a therapeutic stratagem for immunosuppression: Focus on belatacept

Authors Renaud Snanoudj, Carlos Frangié, Benjamin Deroure, Hélène François, Caroline Créput, et al

Published 15 January 2008 Volume 2007:1(3) Pages 203—213

Renaud Snanoudj1,2, Carlos Frangié1,2, Benjamin Deroure1, Hélène François1,2, Caroline Créput1,2, Séverine Beaudreuil1, Antoine Dürrbach1,2, Bernard Charpentier1,2

1Service de Néphrologie et Transplantation Rénale, Hôpital du Kremlin Bicêtre, Assistance Publique Hôpitaux de Paris; Le Kremlin-Bicêtre; France; 2INSERM UMR542, Université Paris-Sud, Villejuif, France

Abstract: The development of immunosuppressive drugs has in recent years been focused on prevention of acute rejection. This has led to an increase in one-year allograft survival. However, these drugs have non-immune effects which contribute to the high incidence of late graft loss, as a consequence of chronic allograft nephropathy, and the death of patients. As an immune-specific alternative to conventional immunosuppressants, new biotechnology tools have been developed; they target the costimulation signal of T-cell activation, particularly by the “classical” B7/CD28 and CD40/CD40L pathways. Here, we review the limitations of current immunosuppressive protocols, the benefits of classical B7/CD28 costimulation blockade, and the first large-scale clinical application of this strategy to human transplantation with belatacept. We will also consider novel costimulatory molecules of the B7/CD28 and TNF/TNF-R families, which appear to be important for the functions of memory and effector T-cells.

Keywords: kidney transplantation, immunosuppressants, costimulation, belatacept, chronic allograft nephropathy, fusion protein

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