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

• Published in: Transplantation Vol. 68; no. 11; p. 1800
• Main Authors: Pierson, 3rd, R N, Chang, A C, Blum, M G, Blair, K S, Scott, M A, Atkinson, J B, Collins, B J, Zhang, J P, Thomas, D W, Burkly, L C, Miller, G G
• Format: Journal Article
• Language: English
• Published: United States 15.12.1999
• Subjects: Animals; Antibodies - therapeutic use; Antibodies, Monoclonal - genetics; CD40 Ligand; Coronary Vessels - drug effects; Coronary Vessels - pathology; Graft Rejection - pathology; Graft Rejection - prevention & control; Graft Survival - drug effects; Heart - physiopathology; Heart Transplantation - immunology; Histocompatibility; Humans; Lymphocyte Culture Test, Mixed; Macaca fascicularis; Membrane Glycoproteins - immunology; Myocardial Contraction; Time Factors; Transplantation, Heterotopic; Transplantation, Homologous; Tunica Intima - pathology; Vasculitis - pathology
• ISSN: 0041-1337
• DOI: 10.1097/00007890-199912150-00026

We evaluated whether a humanized anti-CD154 antibody (hu5c8) prolongs primate cardiac allograft survival. Heterotopic cardiac allografts were performed between MHC class II-mismatched cynomolgus monkeys. Survival was compared between groups treated with a perioperative dosing of hu5c8 (group 1; n=6), sustained dosing with hu5c8 (group 2; n=3), and control regimens (n=4). All recipients received fresh donor-specific transfusions during surgery. 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 often present in hu5c8-treated grafts with stable contractility. Donor-specific mixed lymphocyte reaction was generally preserved. Vasculitis and cellular intimal proliferation were prevalent in rejected grafts but occurred later and were less prevalent in group 2. Anti-CD154 antibody markedly prolongs the survival of cardiac allografts in primates and is well tolerated. Sustained dosing with hu5c8 yielded improved survival and may be associated with a lower incidence of vascular pathology. We conclude that hu5c8 therapy is an effective approach for inhibiting acute cardiac allograft rejection in primates.