Islet allograft survival in nonhuman primates immunosuppressed with basiliximab, RAD, and FTY720.

OBJECTIVE: 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. METHODS: 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 mgon 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.RESULTS: 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 andinsulin-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. CONCLUSIONS: This study provides preliminary evidence of the safety and efficacy of corticosteroid- and calcineurin inhibitor-free immunosuppression ina 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.

作 者：

Wijkstrom M；Kenyon NS；Kirchhof N；Kenyon NM；Mullon C；Lake P；Cottens S；Ricordi C；Hering BJ

刊 名：

Transplantation 

年，卷(期)：

2004V.77(no.6) 

分类号：

 

关键词：

Antibodies, Monoclonal  Diabetes Mellitus, Experimental  Graft Rejection  抗体, 单克隆  糖尿病, 实验性  移植物排斥  移植物存活  免疫抑制剂  胰岛移植

正文语种：

eng 

基金项目：