1. Safe use of anti-CD154 monoclonal antibody in pig islet xenotransplantation in monkeys.
- Author
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Bottino R, Knoll MF, Graeme-Wilson J, Klein EC, Ayares D, Trucco M, and Cooper DK
- Subjects
- Animals, Diabetes Mellitus, Experimental immunology, Graft Rejection immunology, Graft Survival immunology, Heterografts immunology, Immunosuppressive Agents pharmacology, Macaca fascicularis, Swine, Antibodies, Monoclonal pharmacology, CD40 Ligand immunology, Heterografts drug effects, Islets of Langerhans Transplantation immunology, Transplantation, Heterologous methods
- Abstract
Anti-CD154mAb is a powerful co-stimulation blockade agent that is efficacious in preventing rejection, even in xenogeneic settings. It has been used in the majority of successful long-term pig-to-non-human primate islet transplantation models. However, its clinical use was halted as a result of thromboembolic complications that were also observed in preclinical and clinical organ transplantation models. An anti-CD154mAb was administered to 14 streptozotocin-induced diabetic cynomolgus monkey recipients of porcine islets, some of which received the agent for many months. Monkeys were monitored for complications, and blood monitoring was carried out frequently. After euthanasia, multiple biopsies of all organs were examined for histological features of thromboembolism. Anti-CD154mAb prevented rejection of genetically engineered pig islets in all monkeys. No significant complications were attributable specifically to anti-CD154mAb. There was no evidence of thromboembolism in multiple histological sections from all major organs, including the brain. Our data suggest that in diabetic monkeys with pig islet grafts, anti-CD154mAb would appear to be an effective and safe therapy, and is not associated with thromboembolic complications., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2017
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