A novel bispecific DARPin targeting FcγRIIB and FcεRI‐bound IgE inhibits allergic responses

• DOI: 10.1111/all.13109
• Publication Date: 2016-12-20T23:42:47Z
• Authors: F. Zellweger; P. Gasser; D. Brigger; P. Buschor; M. Vogel; A. Eggel
• Keywords: Fragment crystallizable region

Abstract Background Binding of allergen‐specific IgE to its high‐affinity receptor Fcε RI on basophils and mast cells is a central event in the development allergies. Exposure these allergens induces release soluble mediators causing allergic symptoms. The inhibitory low‐affinity IgG Fc‐receptor Fcγ RIIB co‐expressed effector has been implicated negative regulation immediate hypersensitivity responses. In order harvest function this receptor, we aimed select specific binders against generate bispecific molecule simultaneously targeting ‐bound surface cells. Methods We selected ‐specific binding molecules from library designed ankyrin repeat proteins using ribosome display technology. modality was generated by molecular cloning recombinant protein expression. determined characteristics cellular levels SPR , ELISA flow cytometry. potential newly described assessed different degranulation assays ex vivo mouse model passive systemic anaphylaxis. Results demonstrate that DARP ® recognize with high affinity. Furthermore, successfully interferes allergen‐induced cell efficiently inhibits anaphylaxis . Mechanistically, report ‐mediated inhibition activation requires direct ligation an activating receptor. Conclusion ability co‐ligate represents efficient dual‐modality interfere reactions.