Treating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement

• Published in: Nature communications 2018-04, Vol.9 (1), p.1421-15, Article 1421
• Main Authors: Orengo, J. M., Radin, A. R., Kamat, V., Badithe, A., Ben, L. H., Bennett, B. L., Zhong, S., Birchard, D., Limnander, A., Rafique, A., Bautista, J., Kostic, A., Newell, D., Duan, X., Franklin, M. C., Olson, W., Huang, T., Gandhi, N. A., Lipsich, L., Stahl, N., Papadopoulos, N. J., Murphy, A. J., Yancopoulos, G. D.
• Format: Article
• Language: English
• Subjects: 13; 14; 49; 631/250/2152/2153/1291; 631/250/249/2510/9; 631/250/2520; 64; 64/60; 692/308/2779/109/1940; 82/1; 82/103; Adolescent; Adult; Allergens; Allergens - administration & dosage; Allergens - immunology; Allergens - isolation & purification; Allergies; Animal Fur - chemistry; Animal Fur - immunology; Animals; Antibodies; Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal - pharmacology; Binding, Competitive; Blocking; Cats; Complex Mixtures - chemistry; Complex Mixtures - immunology; Crosslinking; Desensitization; Desensitization, Immunologic - methods; Disease Models, Animal; Effector cells; Fc receptors; Female; Glycoproteins - administration & dosage; Glycoproteins - immunology; Glycoproteins - isolation & purification; Humanities and Social Sciences; Humans; Hypersensitivity - immunology; Hypersensitivity - physiopathology; Hypersensitivity - therapy; Immunoglobulin E; Immunoglobulin E - chemistry; Immunoglobulin E - immunology; Immunoglobulin E - metabolism; Immunoglobulin G; Immunoglobulin G - biosynthesis; Immunoglobulin G - pharmacology; Immunotherapy; Male; Mice; Middle Aged; Monoclonal antibodies; multidisciplinary; Protein Binding - drug effects; Receptors; Receptors, IgE - chemistry; Receptors, IgE - immunology; Receptors, IgE - metabolism; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03636-8

Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous. Next, using two potent, pre-selected allergen-blocking monoclonal IgG antibodies against the immunodominant cat allergen Fel d 1, we demonstrate that increasing the IgG/IgE ratio reduces the allergic response in mice and in cat-allergic patients: a single dose of blocking IgG reduces clinical symptoms in response to nasal provocation (ANCOVA, p  = 0.0003), with a magnitude observed at day 8 similar to that reported with years of conventional SIT. This study suggests that simply augmenting the blocking IgG/IgE ratio may reverse allergy. Allergen-specific immunotherapy is used to treat patients affected by acute immunoglobulin E (IgE) responses, but the function mechanism is unclear. Here the authors show that the administration of two cat allergen-specific IgGs reduces allergic responses in mouse models and helps ameliorate clinical symptoms in a phase 1b clinical trial.