Transition of Anti-CD154 Antibody in Renal Transplantation and Prospects for Clinical Application

Abstract

Despite recent improvements in kidney transplantation outcomes, calcineurin inhibitor (CNI)-induced nephrotoxicity is one of the main issues to overcome to prevent renal allograft loss. Costimulatory blockade (CB) is expected to be an alternative agent to CNI. Among many types of CB agents, anti-CD154 antibody has a sufficient effect to suppress immunological response. However, it is not approved for clinical use due to thromboembolism caused by Fc receptor-mediated platelet activation. Although various types of anti-CD154 antibodies have been invented to overcome adverse events, no agents have had a sufficient immunosuppressive effect for allotransplantation. The newly developed anti-CD154 antibody, TNX-1500, was used in a kidney allotransplant model in cynomolgus macaques and was shown to inhibit rejection without a thromboembolism event. Furthermore, AT-1501 also demonstrated similar efficacy. The clinical application of these novel agents is expected to improve the outcome of renal transplantation.