Daclizumab

Abstract

Daclizumab is a humanized monoclonal antibody which binds to the IL-2 receptor on activated lymphocytes and blocks the production of IL-2. Its use is well established in solid organ transplantation as induction therapy, especially in high-risk patients where reduction or delayed dose of standard immunosuppression would be beneficial. It has been used effectively in both 2-dose and 5-dose regimens in conjunction with other standard immunosuppressive agents. The incidence of acute rejection appears reduced without increasing the rates of infection or post-transplant lympho-proliferative disorders. The agent is generally well tolerated in adults and children and there is no need for additional monitoring. Daclizumab has also been used outside the transplant arena in a variety of immune-mediated diseases with limited success.

The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment

“…The effects of intravenous injection of daclizumab in neovascular AMD are being assessed in a phase II clinical trial 88. Daclizumab is reported to be relatively well tolerated with virtually no serious adverse effects following intravenous and subcutaneous injection 99,100. Daclizumab may become a promising adjunctive therapy in neovascular AMD, especially for patients who do not respond to the conventional anti-VEGF agents.…”

Piperine blocks interleukin-2-driven cell cycle progression in CTLL-2 T lymphocytes by inhibiting multiple signal transduction pathways

“…IL-2 has been successfully targeted in vivo using daclizumab and basiliximab, which are monoclonal antibodies (Ab) that inhibit IL-2 signaling by binding to and blocking the a chain (CD25) of the high affinity IL-2 receptor (IL-2R) (Waldmann, 2007). Daclizumab and basiliximab are currently used to prevent transplant rejection (Mottershead and Neuberger, 2007;Ramirez and Marino, 2007) and daclizumab has shown promise in the treatment of multiple sclerosis (Wynn et al, 2010). However, these monoclonal Ab are costly, have to be administered by injection, and there is a risk that repeated administration will induce neutralizing Ab or cause anaphylaxis (Baudouin et al, 2003;Buttmann and Rieckmann, 2008).…”

Human Framework Adaptation of a Mouse Anti-Human IL-13 Antibody

“…9 In subsequent work, Queen et al 10 humanized the first antibody approved by the Food and Drug Administration for therapeutic use in the United States, termed daclizumab, now with wellestablished indication for organ transplantation. 11 Daclizumab was generated by identifying the human framework regions (FRs) with the highest level of homology to the mouse antibody sequence. Mouse CDRs were then grafted onto human FRs together with a set of key mouse amino acids outside the CDRs identified as interacting with the CDRs or the antigen (i.e., backmutations).…”