Treating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement
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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.
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The monoclonal antibody regimen REGN1908/1909 demonstrated significant symptom relief and durable efficacy in a phase Ib clinical trial.
“The monoclonal antibody regimen REGN1908/1909 demonstrated significant symptom relief and durable efficacy in a phase Ib clinical trial [161].”
From Advance in Managing Indoor Cat Allergen Proteins: Molecular Insights, Detection, and Control (2025) · cites this paper as [161]
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Pechsrichuang, P., Namwongnao, S., & Jacquet, A. (2020) · Allergy Asthma and Immunology Research · doi:10.4168/aair.2021.13.1.23 · Cited by 15 · see citing works
- 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.
- Affiliations
- Regeneron (United States) (US)
- Corresponding author
- Orengo, J. M.
- ORCID
- Venue
- Nature Communications
- Published
- 2018-04-12
- Volume
- 9
- Issue
- 1
- Pages
- 1421-1421
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5897525
- OpenAlex
- W2797705783
- Cited by
- 237
- References
- 68
- Citations by year
- 2026: 17 · 2025: 22 · 2024: 32 · 2023: 36 · 2022: 24 · 2021: 35 · 2020: 37 · 2019: 24 · 2018: 10
- FWCI
- 23.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- Howard Hughes Medical Institute (DE-AC02-05CH11231)
- U.S. Department of Energy (-AC02-05CH11231, Contract No. DE-AC02-05-CH11231, 05CH11231, No. DE-AC02-05-CH11231, DE AC02 05CH11231, DE-AC02-)
- Regeneron Pharmaceuticals
- National Institutes of Health (DE-AC02–05CH11231)
- Office of Science (No. DE-AC02- 05-CH11231, DEAC02–05CH11231, AC02-05CH11231, DE-AC02, Contract No. DE-AC02-05CH11231)
- National Institute of General Medical Sciences (DE-AC02-05CH11231)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- cat allergy, Fel d 1, allergen-specific IgG, monoclonal antibodies, allergen immunotherapy, allergen sensitization, nasal provocation, allergic airway inflammation
- MeSH terms
- Animal Fur, Adolescent, Adult, Allergens, Animals, Antibodies, Monoclonal, Binding, Competitive, Cats, Desensitization, Immunologic, Disease Models, Animal, Female, Glycoproteins, Humans, Hypersensitivity, Immunoglobulin E, Immunoglobulin G, Male, Middle Aged, Protein Binding, Receptors, IgE, Complex Mixtures, Mice
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