title: Novel genetically-humanized mouse model established to evaluate efficacy of therapeutic agents to human interleukin-6 receptor.
abstract: 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.
authors: Chugai Pharmaceutical Co. Ltd., Research Division , 1-135, Komakado, Gotemba, Shizuoka, Japan.
authors: Otoya
authors: O
authors: Ueda
authors: Hiromi
authors: H
authors: Tateishi
authors: Yoshinobu
authors: Y
authors: Higuchi
authors: Etsuko
authors: E
authors: Fujii
authors: Atsuhiko
authors: A
authors: Kato
authors: Yosuke
authors: Y
authors: Kawase
authors: Naoko A
authors: NA
authors: Wada
authors: Takanori
authors: T
authors: Tachibe
authors: Mami
authors: M
authors: Kakefuda
authors: Chisato
authors: C
authors: Goto
authors: Makoto
authors: M
authors: Kawaharada
authors: Shin
authors: S
authors: Shimaoka
authors: Kunihiro
authors: K
authors: Hattori
authors: Kou-Ichi
authors: K
authors: Jishage
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology* / Q000627:therapeutic use; D005871:Castleman Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D055879:Gene Knock-In Techniques; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019947:Receptors, Interleukin-6 / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C502936:tocilizumab
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