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

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

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Gasser, Pascal; Guntern, Pascal Martin; Brigger, Daniel; Zbären, Noemi and Eggel, Alexander

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Springer Nature

Language:

English

Submitter:

Lee-Anne Brand

Date Deposited:

21 Jan 2020 16:01

Last Modified:

26 Jan 2020 02:49

Publisher DOI:

10.1038/s41467-019-13815-w

PubMed ID:

31913280

BORIS DOI:

10.7892/boris.138505

URI:

https://boris.unibe.ch/id/eprint/138505

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