100 day cardiac xenograft survival in porcine-to-primate model

A series of experiments were performed to achieve prolonged cardiac xenograft survival using novel immunosuppressive and management techniques. A model of abdominal heterotopic heart transplantation in a porcine-to-baboon model was used. Donor hearts were from pigs transgenic for the human complement regulatory protein CD46. The immunosuppressive regimen was not cyclophosphamide based, but rather included currently used clinical immunosuppressants in therapeutic doses including FK506, Rapamycin, corticosteroids, anti-CD20 monoclonal antibody, and NEX1285, an alpha-Gal-PEG polymer. Median survival in this experiment exceeded 30 days with current ongoing maximum survival of 100 days. Confirmation of cardiac function was by echocardiography, measurement of EKG amplitudes as well as by palpation. The omission of high-dose induction with cyclophosphamide dramatically reduced infective complications. The immunosuppressive regimen was well tolerated by recipients. These results, including the longest survival to date of a cardiac xenograft, offer real encouragement to ongoing research in cardiac xenotransplantation.