Comparative Evaluation of [alpha]CD40 (2C10R4) and [alpha]CD154 (5C8H1 and IDEC-131) in a Nonhuman Primate Cardiac Allotransplant Model.

Background: Specific blockade of T cell costimulation pathway is a promising immunomodulatory approach being developed to replace our current clinical immunosuppression therapies. The goal of this study is to compare results associated with 3 monoclonal antibodies directed against the CD40/CD154 T cell costimulation pathway. Methods: Cynomolgus monkey heterotopic cardiac allograft recipients were treated with either IDEC-131 (humanized [alpha]CD154, n=9), 5C8H1 (mouse-human chimeric [alpha]CD154, n=5), or 2C10R4 (mouse-rhesus chimeric [alpha]CD40, n=6) monotherapy using a consistent, comparable dosing regimen for 3 months after transplant. Results: Relative to the previously reported IDEC-131 treated allografts, median survival time (MST 35+/-31 days) was significantly prolonged in both 5C8H1 (142+/-26, p

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