Daclizumab

Summary

Daclizumab is a humanized IgG1 monoclonal antibody directed against CD25 (IL-2 receptor), which is usually expressed on activated lymphocytes and regulatory T cells, and was the first humanized mAb for renal organ transplantation. Functioning as an IL-2 receptor antagonist, it binds with high affinity to the Tac subunit of the high-affinity IL-2 receptor complex. The development of daclizumab heralded a new age for monoclonal antibodies in the prevention of organ rejection and represented a step forward in establishing humanized monoclonal antibody technology as an integral part of the immunosuppressive regimen. Licensing of daclizumab in the US in 1997 was followed by licensing of the similarly targeted, chimeric monoclonal antibody basiliximab in 1998.

Daclizumab is indicated for the prophylaxis of acute organ rejection in renal transplant patients when used in combination with cyclosporine and corticosteriods.

Daclizumab is reported to offer significantly reduced acute rejection at 6 months, as well as improved patient survival without increased incidence of lymphoma at 3-year followup. Initially, adverse effects appeared similar to placebo, but subsequent cardiac transplantation trials showed an associated increased mortality when daclizumab was used in combination with other immunosuppressives including cyclosporine, mycophenolate mofetil, and corticosteroids. In 2003, the FDA issued MedWatch warnings regarding this risk as well as post-marketing observations of hypersensitivity reactions.  

Brand Name

Zenapax

Other Names

None

Molecular Target

CD25 (IL-2Rα)

Molecular Structure

humanized IgG1 monoclonal antibody

Licensed Indication, Major Target Diseases

renal allograft rejection

Manufacturer/Distributor

PDL
Roche

References