Inhibition of ongoing allergic reactions using a novel anti-IgE DARPin-Fc fusion protein.

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.

• Authors: A Eggel, P Buschor, M J Baumann, P Amstutz, B M Stadler, M Vogel
• Journal: Allergy (Allergy) Vol. 66 Issue 7 Pg. 961-8 (Jul 2011) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 21272035 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• ANKRD23 protein, human
• Allergens
• Antibodies, Anti-Idiotypic
• Muscle Proteins
• Nuclear Proteins
• Receptors, Fc
• Receptors, IgE
• Receptors, IgG
• Recombinant Fusion Proteins
• anti-IgE antibodies
• Immunoglobulin E

Topics

• Allergens (immunology)
• Antibodies, Anti-Idiotypic (immunology)
• Basophils (immunology)
• Cell Degranulation (immunology)
• Humans
• Hypersensitivity (drug therapy, immunology)
• Immunoglobulin E (immunology)
• Muscle Proteins (genetics, metabolism, therapeutic use)
• Nuclear Proteins (genetics, metabolism, therapeutic use)
• Receptors, Fc (genetics, immunology, metabolism, therapeutic use)
• Receptors, IgE (genetics, immunology, metabolism, therapeutic use)
• Receptors, IgG (genetics, immunology, metabolism, therapeutic use)
• Recombinant Fusion Proteins (genetics, metabolism, therapeutic use)