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


  • Edited by: Reto Crameri

Dr. Monique Vogel, University Institute of Immunology, University of Bern, Inselspital, Sahlihaus 2, 3010, Bern, Switzerland.
Tel.: +41 (0)31 632 03 34
Fax: +41 (0)31 381 57 35


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.