The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab
| Autor: | Daniel Brigger, Rahel Ruppli, Pascal Guntern, Theodore S. Jardetzky, Alexander Eggel, Svetlana S. Tarchevskaya, Silke Kleinboelting, Noemi Zbären, Pascal Gasser, Christoph Heusser |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Allergy Science General Physics and Astronomy Translational immunology Mice Transgenic 610 Medicine & health Omalizumab Immunoglobulin E Antibodies Monoclonal Humanized General Biochemistry Genetics and Molecular Biology Epitope Article Antibodies 03 medical and health sciences Mice 0302 clinical medicine In vivo Anti-Allergic Agents medicine Hypersensitivity Animals Humans lcsh:Science X-ray crystallography B-Lymphocytes Multidisciplinary biology Chemistry Receptors IgE CD23 General Chemistry 3. Good health Antibodies Anti-Idiotypic Basophils Mice Inbred C57BL Basophil activation 030104 developmental biology 030228 respiratory system Immunology Monoclonal biology.protein lcsh:Q Antibody medicine.drug |
| Zdroj: | 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 Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020) Nature Communications |
| Popis: | 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. Immunoglobulin E (IgE) plays a central role in allergic responses, yet therapeutic targeting of IgE with antibodies such as omalizumab is met with various limitations. Here the authors characterize the molecular properties and crystal structure of a new anti-IgE antibody, ligelizumab, for mechanistic insights related to its enhanced suppression activity. |
| Databáze: | OpenAIRE |
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