AACR 2021: Humanized IL6/hIL6R mouse model supports the evaluation of therapeutic drug candidates targeting human IL6 and IL6 receptor

AACR 2021: Humanized IL6/hIL6R mouse model supports the evaluation of therapeutic drug candidates targeting human IL6 and IL6 receptor

Author: Leila Kokabee, Yichao Chen, Linlin Wang, Xiaohan Zhang, Xiaofei Zhou, Qingcong Lin, Zhaoxue (Luke) Yu

Interleukin 6 (IL-6) gene encodes a cytokine that functions in inflammation and the maturation of B cells and is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in the immune response. Evidence of recent research shows blockade of IL-6 and IL-6 receptor interaction can offer a broader therapeutic strategy for various diseases included in acute systemic and chronic inflammatory diseases. The development of humanized mouse model can greatly support preclinical evaluation of human IL6 and IL6 receptor therapeutic drugs.

To evaluate the efficacy of IL-6 and IL-6R therapeutic drug candidates, Biocytogen has generated a double humanized B-hIL6/hIL6R mouse model. In this model, the mouse Il6 gene that encodes the full length was replaced with the corresponding human sequences and the CDS of human IL6R gene was inserted into the mouse Il6r gene in B-hIL6/hIL6R mice. Human IL6 or IL6R protein expression was detected in homozygous B-hIL6/hIL6R mice by species-specific IL6 ELISA kit, also evaluated by flow cytometry. In efficacy study of anti-human IL6 antibodies in B-hIL6/hIL6R mice with collagen induced arthritis (CIA), the IL6 antibody treatment reversed the disease progression by decreasing the total clinical score compared to the control group. The efficacy suggests that the B-hIL6/hIL6R mouse model is an effective tool for in vivo efficacy study in the development of IL6 and IL6R antibodies which provide a promising potential in future human clinical trials.

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