C1-inhibitor for treatment of acute vascular xenograft rejection in cynomolgus recipients of h-DAF transgenic porcine kidneys

At present, the major barrier to successful discordant xenotransplantation of unmodified or complement regulator transgenic porcine xenografts is acut e vascular xenograft rejection (AVR). AVR is associated with the intragraft deposition of induced recipient xenoreactive antibodies and subsequent com plement activation. In a life-supporting pig to primate kidney xenotranspla ntation setting using hDAF transgenic donor organs and postoperative immuno suppression. episodes of AVR were either treated with boluses of cyclophosp hamide and steroids or with the same regimen supplemented by a three-day co urse of C1-Inhibitor, a multifunctional complement regulator. In 8 Out of 1 0 animals stable initial graft function was achieved; in all animals one or more episodes of AVR were observed. When, in 4 animals, Cl-Inhibitor was a dded to the standard anti-rejection treatment regimen I AVR was successfull y reversed in 6 out of 7 episodes, while in another group of 4 animals rece iving the standard anti-rejection treatment 0 Out of 4 episodes of AVR resp onded to treatment. Response to anti-rejection treatment was associated wit h a significant increase in recipient survival time. We conclude that AVR o f h-DAF transgenic porcine kidneys can be Successfully treated by additiona l short-tel-In fluid phase complement inhibition.