Edited by: Reto Crameri
Inhibition of ongoing allergic reactions using a novel anti-IgE DARPin-Fc fusion protein
Version of Record online: 28 JAN 2011
© 2011 John Wiley & Sons A/S
Volume 66, Issue 7, pages 961–968, July 2011
How to Cite
Eggel, A., Buschor, P., Baumann, M. J., Amstutz, P., Stadler, B. M. and Vogel, M. (2011), Inhibition of ongoing allergic reactions using a novel anti-IgE DARPin-Fc fusion protein. Allergy, 66: 961–968. doi: 10.1111/j.1398-9995.2011.02546.x
- Issue online: 1 JUN 2011
- Version of Record online: 28 JAN 2011
- Accepted for publication 29 December 2010
- allergy treatment;
- basophils degranulation;
- Fc receptors;
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.
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 IgG1 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 IgG1 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.