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: |
musculoskeletal diseases
medicine.drug_class Transgene Mice Transgenic Pharmacology Monoclonal antibody Antibodies Monoclonal Humanized Article chemistry.chemical_compound Mice Tocilizumab In vivo Medicine Animals Humans Gene Knock-In Techniques Interleukin 6 Multidisciplinary biology business.industry Interleukin-6 Castleman Disease Receptors Interleukin-6 Mice Inbred C57BL Disease Models Animal chemistry Monoclonal Humanized mouse biology.protein Female Antibody business |
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 |
Externí odkaz: |