Pharmacodynamic study of Dupilumab based on HDM induced asthma model in BALB/c-hIL4hIL4R? humanized mice 4820

Abstract Description Ting wang1, Juan Liang1 1GemPharmatech Co. Ltd., 12 Xuefu Road, Nanjing, 210061, China The IL4/IL4Rα signal pathway is involved in regulating lgE production, chemokine and mucus production and promoting Th2 differentiation; and also play an important role in the initiation and progression of several diseases, such as atopic dermatitis (AD) and asthma. Besides, Dupilumab, a human monoclonal antibody that targets IL4R? has demonstrated a significant clinical efficacy in AD and asthma, indicating that the potential of IL4R? as an attractive target with implications in the treatment of atopic diseases. We have successfully established HDM induced acute asthma model in BALB/c-hIL4/hIL4R? mice, with the phenotypes of a significant increase of lung weight, serum mouse IgE level, the proportion and number of eosinophils in the lung tissues, and increasing lung inflammation scores and significant airway wall thickening. In addition, under the condition of HDM plus exogenous hIL-4 treatment, Dupilumab administered group greatly attenuated these phenotypes, suggesting a significant pharmacodynamic effect of Dupilumab in asthma model. In addition to that, we also have observed a raises in ear skin human IL4 and mouse IL13 mRNA level, serum mouse IgE secretion and skin clinical score based on the OXA induced AD model. Topic Categories Basic Autoimmunity (BA)