The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab.

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Citation

Gasser P, Tarchevskaya SS, Guntern P, Brigger D, Ruppli R, Zbaren N, Kleinboelting S, Heusser C, Jardetzky TS, Eggel A

The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab.

Nat Commun. 2020 Jan 8;11(1):165. doi: 10.1038/s41467-019-13815-w.

PubMed ID
31913280 [ View in PubMed
]
Abstract

Targeting of immunoglobulin E (IgE) represents an interesting approach for the treatment of allergic disorders. A high-affinity monoclonal anti-IgE antibody, ligelizumab, has recently been developed to overcome some of the limitations associated with the clinical use of the therapeutic anti-IgE antibody, omalizumab. Here, we determine the molecular binding profile and functional modes-of-action of ligelizumab. We solve the crystal structure of ligelizumab bound to IgE, and report epitope differences between ligelizumab and omalizumab that contribute to their qualitatively distinct IgE-receptor inhibition profiles. While ligelizumab shows superior inhibition of IgE binding to FcepsilonRI, basophil activation, IgE production by B cells and passive systemic anaphylaxis in an in vivo mouse model, ligelizumab is less potent in inhibiting IgE:CD23 interactions than omalizumab. Our data thus provide a structural and mechanistic foundation for understanding the efficient suppression of FcepsilonRI-dependent allergic reactions by ligelizumab in vitro as well as in vivo.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
LigelizumabImmunoglobulin heavy constant epsilonProteinHumans
Yes
Antibody
Details