Islet allograft survival in nonhuman primates immunosuppressed with basiliximab, RAD, and FTY7201
- 27 March 2004
- journal article
- Published by Wolters Kluwer Health in Transplantation
- Vol. 77 (6) , 827-835
- https://doi.org/10.1097/01.tp.0000116390.76425.20
Abstract
In a preclinical, nonhuman primate islet allotransplant model, the authors evaluated a novel immunosuppressive combination of basiliximab for induction and of RAD and FTY720 for maintenance. Five ABO-compatible and mixed lymphocyte reactivity-mismatched streptozotocin-induced diabetic juvenile cynomolgus monkeys underwent transplantation intraportally with 48-hr cultured 10,000 islet equivalents per kilogram. Induction immunosuppression was with intravenous basiliximab (10 mg on postoperative days 0 and 4). Maintenance immunosuppression was with RAD (everolimus) (0.075 mg/kg per day administered subcutaneously) and FTY720 (0.3 mg/kg per day administered orally), both administered on day -2 through day 180 posttransplant. All five recipients tolerated their transplants and immunosuppressive therapy well, without adverse events or infectious complications. Insulin requirements pretransplant were 2.6 to 4.0 U/kg per day. All recipients became normoglycemic and insulin-independent posttransplant. Posttransplant serum C-peptide levels averaged 2.7 ng/mL (range, 0.6-6.2 ng/mL). Morning blood glucose levels ranged from less than 100 mg/dL to 150 mg/dL. Posttransplant acute C-peptide response to intravenous arginine averaged 1.3 ng/mL (range, 0.23-2.72 ng/mL). In one recipient with subtherapeutic RAD blood levels on day 7 posttransplant, exogenous insulin was resumed 100 days posttransplant; basal C-peptide levels remained positive in this recipient and averaged 2.6 ng/mL. The other four recipients remained insulin-independent for more than 6 months. This study provides preliminary evidence of the safety and efficacy of corticosteroid- and calcineurin inhibitor-free immunosuppression in a relevant preclinical transplant model. These findings provide a strong rationale for evaluating this nondiabetogenic regimen in a clinical trial of islet transplants in type 1 diabetic recipients.Keywords
This publication has 28 references indexed in Scilit:
- The use of basiliximab in solid organ transplantationExpert Opinion on Pharmacotherapy, 2002
- Successful Islet TransplantationDiabetes, 2002
- Treatment with immunotoxinPhilosophical Transactions Of The Royal Society B-Biological Sciences, 2001
- Islet Transplantation in Seven Patients with Type 1 Diabetes Mellitus Using a Glucocorticoid-Free Immunosuppressive RegimenNew England Journal of Medicine, 2000
- PRETREATMENT WITH FTY-720 PROTECTS RENAL ALLOGRAFTS AGAINST PRESERVATION-REPERFUSION INJURY.Transplantation, 2000
- The role of the B7 costimulatory pathway in experimental cold ischemia/reperfusion injury.Journal of Clinical Investigation, 1997
- Islet isolation assessment in man and large animalsActa Diabetologica, 1990
- EFFECT OF CYCLOSPORINE ON IMMUNOLOGICALLY MEDIATED DIABETES IN NONOBESE DIABETIC MICE1Transplantation, 1988
- Toxicologic Evaluation of Streptozotocin (NSC 85998) in Mice, Dogs and MonkeysDrug and Chemical Toxicology, 1980
- Prolongation of Islet Allograft Survival Following in Vitro Culture (24°C) and a Single Injection of ALSScience, 1979