Clinical Use
Molecularly, daclizumab (Zenapax, Chimeric) is an IgG1MAb that binds specifically to the α subunit of the IL-2 receptor(the complete, high-affinity activated IL-2 receptorconsists of interacting α, β, and γ subunits). IL-2 receptorsare expressed on the surfaces of activated lymphocytes,where they mediate lymphocyte clonal expansion and differentiation.Daclizumab is a chimeric protein (90% humanand 10% mouse) IgG1. The MAb targets only recently activatedT cells that have interacted with antigen and have developedfrom their naive form into their activated form. Itis at this time that the IL-2 receptors are expressed. Thehuman amino acid sequences of daclizumab derive fromconstant domains of human IgG, and the variable domainsare derived from the fused Eu myeloma antibody. Themurine sequences derive from CDRs of a mouse anti-IL2αantibody.
The indications for daclizumab are prophylaxis of acuteorgan rejection in patients receiving renal transplants, aspart of an immunosuppressant regimen including cyclosporineand corticosteroids. The mechanism of action isthe same as that of basiliximab.
Metabolism
As an IgG1 monoclonal antibody, daclizumab is expected
to undergo catabolism to peptides and amino acids in
the same manner as endogenous IgG. Daclizumab is not
expected to undergo metabolism by hepatic enzymes such
as CYP isoenzymes.
