ASKP1240, a fully human anti-CD40 monoclonal antibody, prolongs pancreatic islet allograft survival in nonhuman primates.

摘要: A strategy for inhibiting CD40 has been considered as an alternative approach immunosuppression because of undesirable effects anti-CD154 monoclonal antibodies (mAbs). Previously, we demonstrated that ASKP1240, which is a fully human anti-CD40 mAb, significantly prolonged kidney and liver allograft survival in cynomolgus monkeys without causing thromboembolic complications. Herein, evaluated the effect ASKP1240 on pancreatic islet transplantation (PITx) monkeys. Diabetes was induced by total pancreatectomy, allografts were transplanted into liver. Following PITx (8201-12 438 IEQ/kg), blood glucose levels normalized promptly all animals. Control rejected within 9 days (n = 3), whereas (10 mg/kg) given postoperative 0, 4, 7, 11 14 (induction treatment, n 5) graft time (GST) to >15, >23, 210, 250 >608 days, respectively. When (5 administered weekly thereafter up post-PITx 6 months (maintenance 4), GST markedly >96, >115, 523 >607 days. During treatment period, both anti-donor cellular responses development abolished, no serious adverse events noted. appears be promising candidate clinical PITx.