樂音佳文
IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE-downregulation and relieves urticaria symptoms
In this report, we feature the uniqueness of UB-221 that differentiates from omalizumab and ligelizumab:
(a) Free UB-221 binds to CD23-bound IgE and engages CD23 in an unrestricted manner when in multiple mAb:IgE complexed forms, while both ligelizumab and omalizumab are much limited in their indirect binding with CD23.
(b) The differential CD23-interaction profiles correlate with the finding that UB-221 downregulates in greatest level the CD23-mediated IgE neo-synthesis in human PBMCs under co-stimulation by IL-4 and an anti-CD40 antibody.
(c) Moreover, UB-221 binds IgE with a higher affinity than omalizumab and performs superior in IgE neutralization and prevention of basophil degranulation.
(d) UB-221 and ligelizumab neutralize high serum IgE of atopic dermatitis patients with equal strength, while omalizumab is less effective.
(e) In cynomolgus macaques and human IgE (ε, κ)-transgenic hIGHE (immunoglobulin heavy epsilon)-knockin mice, a single dose of UB-221 can induce a rapid, profound reduction of serum IgE.
(f) In addition, UB-221 in the Phase-1 single-dose clinical trial with chronic spontaneous urticaria patients has demonstrated durable disease symptom relief that associates with a rapid reduction in serum free IgE level.