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

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 FcεRI, 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 FcεRI-dependent allergic reactions by ligelizumab in vitro as well as in vivo.

journal_name

Nat Commun

journal_title

Nature communications

authors

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

doi

10.1038/s41467-019-13815-w

subject

Has Abstract

pub_date

2020-01-08 00:00:00

pages

165

issue

1

issn

2041-1723

pii

10.1038/s41467-019-13815-w

journal_volume

11

pub_type

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