Publikationsdatenbank

Recombinant antibodies against equine interleukin 5 to treat insect bite hypersensitivity (2023)

Art

Vortrag

Autoren

Schäckermann, D.

Langreder, N.

Ladel, S.

Roßbach, K.

Bäumer, W. (WE 14)

Hust, M.

Kongress

15th International Congress of the European Association for Veterinary Pharmacology and Toxicology

Bruges, Belgium, 02. – 05.07.2023

Quelle

Journal of veterinary pharmacology and therapeutics

Bandzählung: 46

Heftzählung: S1

Seiten: 47

ISSN: 1365-2885

Sprache

Englisch

Verweise

URL (Volltext): https://onlinelibrary.wiley.com/doi/10.1111/jvp.13206

DOI: 10.1111/jvp.13206

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Insect bite hypersensitivity (IBH) is the most common allergic disease in horses, nevertheless the molecular process and complex interplay between different components of the immune system are not fully understood yet. Symptoms range from pruritus and hair loss to wounds and haemorrhagic crusts, which can be targeted by secondary infections. The disease is characterized as an type I allergy combined with a type IVb allergy with a strong involvement of eosinophils. Cytokine producing TH2 cells play a central role. The main challenge is the absence of a specific and effective treatment, since glucocorticoids show strong side effects. We generated antibodies against interleukin 5 (IL-5), the main activator and regulator of eosinophils as a new and safe treatment option. We used the phage display technology to generate monoclonal antibodies with equine constant domains. These antibodies were produced in mammalian cells and further characterized regarding efficacy and stability. An in vitro inhibition assay was developed in our lab to assess the ability of the antibodies to inhibit the binding of IL-5 to its receptor. Our top antibody shows a successful inhibition of IL-5 binding to its receptor with an IC50 value of 4 nM. Furthermore, the antibody shows a good safety and tolerability in horses. In a first in vivo study we discovered no side effects and found indications for a therapeutic effect. The results of the in vivo data together with the results of the in vitro data allow the conclusion that this antibody is a promising candidate for the treatment of IBH.

Conclusion:
IBH is a relevant disease affecting many horses and its molecular network needs further understanding. We offer a new specific treatment option, targeting IL-5 the main activator and regulator of eosinophils.