Long-term kidney graft survival by delayed T cell ablative treatment in rhesus monkeys.

Background: Tolerance to organ allografts in primates including man has been elusive, although in rodents and pigs tolerance can be achieved to organ allografts with relatively short courses of immunosuppressive treatment. In all varieties of graft acceptance that do not require full-dose maintenance immunosuppression, immunological engagement of donor and recipient and an early unstable period have been observed. On the basis of the hypothesis that elimination of aggressive T cell function should tip the balance in favor of an operationally tolerant state, experiments have been performed in monkeys allowing recipient-donor interaction before T-cell ablation and a short course of immunosuppression.

Pharmacokinetics of cyclosporine in monkeys after oral and intramuscular administration: relation to efficacy in kidney allografting.

In cynomolgus and rhesus monkeys, the dose-normalized exposure of cyclosporine administered orally as microemulsion preconcentrate (Neoral) was lower than that upon intramuscular administration. For oral administration, mean values ( +/- SD) of Cmax, 24-h area-under-the curve (AUC) and 24-h trough level, all normalized for a 1 mg/kg dose, were 20 +/- 9 ng x kg/mg x ml, 210 +/- 70 ng x h x kg/mg x ml and 2.6 +/- 0.

Oral efficacy of the macrolide immunosuppressant SDZ RAD and of cyclosporine microemulsion in cynomolgus monkey kidney allotransplantation.

Background: 40-O-(2-Hydroxyethyl)-rapamycin (SDZ RAD) is a novel, potent, macrolide immunosuppressant. Its efficacy in rodent transplantation models provided the rationale for us to evaluate the compound in a more relevant, large animal transplantation model.

Methods: Life-supporting kidney allotransplantation was performed in cynomolgus monkeys: rejection was inferred from a rise in serum creatinine or urea and was subsequently confirmed by histopathology.

A new reagent for the induction of T-cell depletion, anti-CD3-CRM9.

We have developed a new reagent for inducing in vivo T-cell depletion and have tested this reagent in rhesus monkeys. The reagent is an anti-CD3 epsilon immunotoxin based on a diphtheria toxin binding-site mutant, CRM9. After administration to monkeys, T cells are depleted from both the blood and lymph node compartments to < 1% of their initial values.