Prevention of Rejection in Cardiac Transplantation by Blockade of the Interleukin-2 Receptor with a Monoclonal Antibody

Abstract

Induction therapy with daclizumab safely reduces the frequency and severity of cardiac-allograft rejection during the induction period.

Effect of Anti‐IL‐2Rα Antibody on IL‐2‐induced Jak/STAT Signaling

“…Daclizumab effectively prevents rejection of renal and cardiac allografts (10,20) and its positive clinical effect has been attributed to inhibition of clonal T-cell expansion (21). The molecular Confocal microscopy was used to determine the localization of daclizumab molecules in PHA blasts that were pretreated with daclizumab and then examined either 1 or 18 h after treatment.…”

Daclizumab (anti-Tac, Zenapax) in the treatment of leukemia/lymphoma

“…On the basis of the efficacy in these multicenter trials and the lack of associated increase in toxicity, in 1997 the FDA provided marketing clearance for the use of daclizumab in the prevention of acute kidney transplant rejection. In subsequent studies, in clinical trials involving a large group of recipients, daclizumab provided a reduction in the rejection episodes in patients receiving renal, liver, cardiac and pancreatic islet transplants (Beniaminovitz et al, 2000;Eckhoff et al, 2000;Shapiro et al, 2000).…”

Immunosuppressive Therapy After Cardiac Transplantation

“…Saturation maintained with basiliximab for 4 to 6 weeks, with daclizumab for about 90 to 120 days. It was shown that anti-IL-2 receptor antibodies when combined with standard triple druge regime for induction therapy compared to placebo reduces rejection episodes [19,20]. In a trial using daclizumab 1 mg per kg within 24 hours after HTx and repeated every two weeks www.intechopen.com Cardiac Transplantation 6 for a total dosage of five, less rejection rates compared to placebo were seen [19].…”

“…The triple-drug protocol, even if modified (many centres skipping corticosteroids after a certain time) is still used around the globe. Adding a forth drug to the regime has been reported but became not standard [19,89].…”

“…It was shown that anti-IL-2 receptor antibodies when combined with standard triple druge regime for induction therapy compared to placebo reduces rejection episodes [19,20]. In a trial using daclizumab 1 mg per kg within 24 hours after HTx and repeated every two weeks www.intechopen.com Cardiac Transplantation 6 for a total dosage of five, less rejection rates compared to placebo were seen [19]. In a later study it was shown that two doses of daclizumab are similar effective in preventing rejection as five doses, with no negative effects on patient survival [21].…”