Costimulation blockade in kidney transplantation: an update.

In the setting of solid-organ transplantation, calcineurin inhibitor (CNI)-based therapy remains the cornerstone of immunosuppression. However, long-term use of CNIsis associated with some degree of nephrotoxicity. This has led to exploring the blockadeof some costimulation pathways as an efficient immunosuppressive tool instead of using CNIs. The only agent already in clinical use and approved by the health authorities for kidney-transplant patients is belatacept (Nulojix): a fusion protein that interferes with CTLA-4. Belatacep thas been demonstrated to be as efficient as cyclosporine-based immunosuppression and is associated with significantly better renal function, i.e., no nephrotoxicity. However, in the immediate posttransplant period, significantly more mild/moderate episodes of acute rejection have been reported, caused by the CTLA-4 pathway having an inhibitory effect on the allo-immune response. This has led to the development of antibodies that target CD28. The most advanced is FR104: it has shown promise in nonhuman primate models of autoimmune diseases and allo-transplantation. In addition, research into blocking the CD40-CD154 pathway is underway. A phase-II studytesting ASK1240, i.e. anti-CD40 antibody has been completed and the results are pending. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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