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Inhibition of ongoing allergic reactions using a novel anti‐IgE DARPin‐Fc fusion protein
Author(s) -
Eggel A.,
Buschor P.,
Baumann M. J.,
Amstutz P.,
Stadler B. M.,
Vogel M.
Publication year - 2011
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2011.02546.x
Subject(s) - immunoglobulin e , omalizumab , degranulation , basophil activation , fusion protein , immunology , basophil , receptor , allergy , antibody , allergen , chemistry , medicine , biochemistry , recombinant dna , gene
To cite this article: Eggel A, Buschor P, Baumann MJ, Amstutz P, Stadler BM, Vogel M. Inhibition of ongoing allergic reactions using a novel anti‐IgE DARPin‐Fc fusion protein. Allergy 2011; 66 : 961–968. Abstract Background: Aggregation of the high‐affinity IgE receptor (FcεRI) with the low‐affinity IgG receptor (FcγRIIb) on basophils or mast cells has been shown to inhibit allergen‐induced cell degranulation. Molecules cross‐linking these two receptors might therefore be of interest for the treatment of allergic disorders. Here, we demonstrate the generation of a novel bispecific fusion protein efficiently aggregating FcεRI‐bound IgE with FcγRIIb on the surface of basophils to prevent pro‐inflammatory mediator release. Methods: Alternative binding molecules recognizing receptor‐bound human IgE were selected from DARPin (designed ankyrin repeat protein) libraries. One of the selected DARPins was linked to the Fc‐part of a human IgG 1 antibody for binding to FcγRIIb. Results: The resulting anti‐IgE DARPin‐Fc fusion protein was not anaphylactogenic and inhibited allergen‐induced basophil activation in whole blood assays. Both binding moieties of the fusion protein, namely the anti‐IgE DARPin as well as the IgG 1 Fc‐part, were required to achieve this inhibitory effect. Most importantly, inhibition was faster and more efficient than with Omalizumab, a humanized anti‐IgE antibody currently used for the treatment of severe asthma. Conclusion: This novel anti‐IgE DARPin‐Fc fusion protein might represent a potential drug candidate for preventive or immediate treatment of allergic reactions.