INHIBITION OF COMPLEMENT, EVOKED ANTIBODY, AND CELLULAR-RESPONSE PREVENTS REJECTION OF PIG-TO-PRIMATE CARDIAC XENOGRAFTS

Complement (C) inhibition alone using a recombinant soluble form of co mplement receptor type 1 (sCR1) prevents hyperacute rejection but not subsequent irreversible accelerated acute rejection of dis cordant pig -to-cynomolgus monkey cardiac xenografts, which occurs within 1 week. To inhibit accelerated acute rejection, which is associated with a ris e in serum xenoreactive antibody (Ab) and a cellular infiltrate, tripl e therapy with standard immunosuppressive agents (cyclosporine, cyclop hosphamide, and steroids [CCS]) was combined with continuous C inhibit ion using sCR1. Each of two monkeys that re ceived sCR1 + CCS showed m inimal evidence of rejection when killed on days 21 and 32 in comparis on to a monkey that received sCR1 + subtherapeutic CCS (rejected at 11 days) and a control that received CCS alone (rejected at 38 min). Pro longed xenograft survival was associated with low Ab levels and a mini mal cellular infiltrate, suggesting that combined inhibition of C, xen oreactive Ab responses, and cellular immunity may be a useful approach in overcoming the immune barriers to discordant xenotransplantation.