Daclizumab
Humanized anti-CD25 antibody for transplant rejection prevention and multiple sclerosis (withdrawn due to safety concerns).
Chemical Identity
| Property | Value |
|---|---|
| Molecular Weight | ~144 kDa |
| Structure | Humanized IgG1 monoclonal antibody |
| Target | CD25 (IL-2R alpha chain) |
| CAS Number | 152923-56-3 |
| Route | IV (transplant), SC (MS) |
Structure
Daclizumab (Zenapax, Zinbryta) is a humanized IgG1 monoclonal antibody targeting CD25. The complementarity-determining regions (CDRs) from a murine anti-CD25 antibody were grafted onto a human IgG1 framework, reducing immunogenicity while maintaining binding affinity.
Mechanism of Action
Daclizumab binds CD25 on activated T cells, blocking IL-2 binding and preventing IL-2-mediated T-cell proliferation. In MS, it may also expand regulatory CD56bright NK cells that suppress autoimmune T cells. It selectively targets activated immune cells without broad immunosuppression.
Clinical Applications
- Kidney transplant: Induction therapy (Zenapax, discontinued)
- Multiple sclerosis: Relapsing MS (Zinbryta, withdrawn 2018)
- Uveitis: Investigational
- Type 1 diabetes: Investigational (preserving beta-cell function)
- Withdrawn: Due to immune-mediated encephalitis and hepatitis
Pharmacokinetics
- Half-life: 20 days
- Tmax: End of infusion
- CD25 saturation: >90% for 120 days
- Dosing: 1 mg/kg IV every 2 weeks (transplant)
- Route: IV, SC
Safety and Side Effects
Infections, immune-mediated hepatitis, encephalitis (fatal cases led to withdrawal of Zinbryta), skin reactions, and thrombocytopenia. Zinbryta withdrawn from market in 2018 due to inflammatory brain and liver adverse events.
References
- Vincenti, F., et al. (1998). Daclizumab for kidney transplant. New England Journal of Medicine, 338, 161-165.
- Kappos, L., et al. (2016). Daclizumab for MS (DECIDE). New England Journal of Medicine, 375, 2200-2211.
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