Novel genetically-humanized mouse model established to evaluate efficacy of therapeutic agents to human interleukin-6 receptor

Autor: Takanori Tachibe, Otoya Ueda, Etsuko Fujii, Naoko A. Wada, Mami Kakefuda, Makoto Kawaharada, Yosuke Kawase, Shin Shimaoka, Kou-ichi Jishage, Hiromi Tateishi, Yoshinobu Higuchi, Kunihiro Hattori, Atsuhiko Kato, Chisato Goto
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/srep01196
Popis: For clinical trials of therapeutic monoclonal antibodies (mAbs) to be successful, their efficacy needs to be adequately evaluated in preclinical experiments. However, in many cases it is difficult to evaluate the candidate mAbs using animal disease models because of lower cross-reactivity to the orthologous target molecules. In this study we have established a novel humanized Castleman's disease mouse model, in which the endogenous interleukin-6 receptor gene is successfully replaced by human IL6R, and human IL6 is overexpressed. We have also demonstrated the therapeutic effects of an antibody that neutralizes human IL6R, tocilizumab, on the symptoms in this mouse model. Plasma levels of human soluble IL6R and human IL6 were elevated after 4-week treatment of tocilizumab in this mouse model similarly to the result previously reported in patients treated with tocilizumab. Our mouse model provides us with a novel means of evaluating the in vivo efficacy of human IL6R-specific therapeutic agents.
Databáze: OpenAIRE