ISLET ALLOGRAFT SURVIVAL IN DIABETIC MONKEYS AFTER ANTI-CD154, DST, AND DELAYED REPAMYCIN TREATMENT

Abstract

O202 Aims: Pre-clinical studies in non-human primates are useful to evaluate the safety and efficacy of new approaches for clinical islet transplantation. Previously we have shown that combined treatment with anti-CD40L, DST and rapamycin (RPM) can prolong graft survival for >300 days. However, DST, anti-CD40L and RPM needed to be given 3 -7 days before islet transplantation for the treatment to be maximally effective. In this study we tested the effect of DST and anti-CD40L given on the day of transplantation followed by delayed RPM, a protocol more practical in clinical application. Methods: Fifteen islet transplants infused into the portal vein were performed in streptozotocin induced diabetic cynomolgus monkeys. RPM was stopped on day 28 in all recipients. The RPM dose of 1mg/kg produced therapeutic blood levels of >10 ng/ml in our animals. Results:Figure* Functional Survival= time to FBG>250mg/dl for >4 days in the absence of infection. ** C-Peptide = level during period of insulin independence vs. level upon return to insulin dependence. *** Histological Findings at time of autopsy. Conclusions: Survival of allogeneic islet transplants can be prolonged for up to 145 days in monkeys using post-transplant immunosuppression (DST and anti-CD40L given on day 0 and RPM for only 28 days starting on day 0. Delayed RPM prolonged islet graft survival vs. RPM given on day 0 (d 15). However, this protocol did not prevent chronic rejection of the islets, and it was not as effective as the treatment protocol started 7 days before islet transplantation.