Gasser, Pascal; Tarchevskaya, Svetlana S; Guntern, Pascal Martin; Brigger, Daniel; Ruppli, Rahel; Zbären, Noemi; Kleinboelting, Silke; Heusser, Christoph; Jardetzky, Theodore S; Eggel, Alexander (2020). The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab. Nature Communications, 11(1), p. 165. Springer Nature 10.1038/s41467-019-13815-w
|
Text
s41467-019-13815-w.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (4MB) | Preview |
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.
Actions (login required)
 |
Edit item |