AACR 2021: Humanized IL17A/IL17F mouse model provides a preclinical tool for the evaluation of therapeutic drugs targeting to IL-17 pathway

AACR 2021: Humanized IL17A/IL17F mouse model provides a preclinical tool for the evaluation of therapeutic drugs targeting to IL-17 pathway

Author: Leila Kokabee, Yichao Chen, Chong Li, Xiaofei Zhou, Qingcong Lin, Chaoshe Guo, Zhaoxue (Luke) Yu

Interleukin 17 (IL-17) is described as a pro-inflammatory cytokine produced by activated CD4 cells. Evidence shows that IL-17 is highly up-regulated at sites of inflammatory tissues of autoimmune diseases and amplifies the inflammation through synergy with other cytokines, such as TNF (tumor necrosis factor) α. Therefore, targeting IL-17/IL-17R, IL-17-producing pathways or IL-17-mediated signaling pathways can be considered for future therapy in autoimmune diseases.

 

To evaluate the efficacy of IL17A and IL17F antibodies, we generated a double humanized B-hIL17A/hIL17F mouse in Biocytogen. In this model, the sequences encoding the extracellular domains of the mouse IL17A gene and the IL17F gene were replaced with the corresponding human sequences. IL17A and IL17F protein expression was detected in B-hIL17A/hIL17F mice by ELISA using a species-specific IL17A and IL17F ELISA kits. In efficacy study of anti-human IL17A and IL17F antibody with psoriasis model induced in B-hIL17A/hIL17F mice, mice were treated with different dose of bimekizumab produced in house. Erythema and scaling score of the skin was significantly reduced compared with non-treatment group. The results suggest B-hIL17A/hIL17F mouse model is an effective tool for in vivo efficacy evaluation, which may represent a promising model for screening IL17 related drug candidates for the treatment of psoriasis disease.

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