Introduction: Despite achieving longest reported graft survival by us via anti CD154 mediated co stimulation blockade, many coagulation disorders were witnessed due to direct binding of anti CD154 with CD154 expressed on the platelets. The overall recipient survival was markedly affected by this complication. In this experiment we used anti CD40 antibodies, expressed as either mouse or non human primate (rhesus) recombinant antibodies, to see if we could get the similar graft survival without the coagulopathies associated with anti CD154 treatment. Methods: Two different clones of anti CD40 (25 mg/Kg) were used for the maintenance therapy. One clone, 3A8 (mouse IgG2b) has been shown to activate B-lymphocytes in some primate species. The 2nd clone, 2C10 (mouse/rhesus chimeric IgG4), had entirely antagonistic activity, and blocked CD154-mediated activation of human and rhesus B cells in vitro. Besides the anti CD40 antibody, baboons received induction regimen of anti CD20, cobra venom factor, thymoglobulin and maintenance regimen of MMF and steroids. GalKO CD46Tg pigs served as the donors. Results: The thrombotic complications seen with anti CD154 were effectively avoided but the graft survival, though extended, was not as long as observed with anti CD154. The 3A8 antibody group (n=3) had the graft survival of 21,28 and 21 days respectively and the graft survival in 2C10 group (n=6) was 30, 60, 40, 146, 149, 107days respectively. All the grafts rejected and were explanted. None of the recipient baboons died in either group and stayed healthy throughout the graft survival. The platelet number, hematocrit and hemoglobin remained stable throughout the experiment. Conclusion: Neither clone of anti CD40 antibody at the current dose induced apparent coagulopathies but the graft survival was significantly shorter compared to CD154 group. Affinity of the 2C10 clone for baboon CD40 is currently being measured to help determine the appropriate dose of the antibody in this species.
To cite this abstract in AMA style:Singh A, Corcoran P, Lewis B, Hoyt R, Thomas M, Eckhaus M, Mayhew C, Clark T, Reimann K, Ayares D, Horvath K, Mohiuddin M. Complication Free Heterotopic Cardiac Xenograft Survival by Anti CD40 Antibody Mediated Co-Stimulation Blockade [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/complication-free-heterotopic-cardiac-xenograft-survival-by-anti-cd40-antibody-mediated-co-stimulation-blockade/. Accessed April 8, 2020.
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