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

Richard N. Pierson, Andrew C. Chang, Matthew G. Blum, Kelly S.A. Blair, Margie A. Scorr, James B. Atkinson, Brendan J. Collins, Jian Ping Zhang, David W. Thomas, Linda C. Burkly, Geraldine G. Miller

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Abstract

Background. We evaluated whether a humanized anti-CD154 antibody (hu5c8) prolongs primate cardiac allograft survival. Methods. 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. 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 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. Conclusions. 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.

Original languageEnglish (US)
Pages (from-to)1800-1805
Number of pages6
JournalTransplantation
Volume68
Issue number11
DOIs
StatePublished - Dec 15 1999

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ASJC Scopus subject areas

  • Transplantation

Cite this

Pierson, R. N., Chang, A. C., Blum, M. G., Blair, K. S. A., Scorr, M. A., Atkinson, J. B., Collins, B. J., Zhang, J. P., Thomas, D. W., Burkly, L. C., & Miller, G. G. (1999). Prolongation of primate cardiac allograft survival by treatment with anti-CD40 ligand (CD154) antibody. Transplantation, 68(11), 1800-1805. https://doi.org/10.1097/00007890-199912150-00026