Prolongation of primate cardiac allograft survival by treatment with anti-CD40 ligand (CD154) antibody

Background We evaluated whether a humanized anti-CD154 antibody (hu5c8) pro longs primate cardiac allograft survival. Methods. Heterotopic cardiac allografts were performed between MHC class II -mismatched cynomolgus monkeys. Survival was compared between groups treate d with a perioperative dosing of hu5c8 (group I; n=6), sustained dosing wit h hu5c8 (group 2; n=3), and control regimens (n=4). All recipients received fresh donor-specific transfusions during surgery. Results, Median graft survival was 49 days (range 14 to 56) in group 1 and 106 days (range 56 to 245) in group 2, compared with 5 days (range 5 to 6) for controls (P<0.05 for all comparisons). Lymphocytic infiltrates were oft en present in hu5c8-treated grafts with stable contractility, Donor-specifi c mixed lymphocyte reaction was generally preserved. Vasculitis and cellula r intimal proliferation were prevalent in rejected grafts but occurred late r and were less prevalent in group 2. Conclusions. Anti-CD154 antibody markedly prolongs the survival of cardiac allografts in primates and is well tolerated. Sustained dosing with hu5c8 y ielded improved survival and may be associated with a lower incidence of va scular pathology. We conclude that hu5c8 therapy is an effective approach f or inhibiting acute cardiac allograft rejection in primates.