Development of new anti-TNF therapy

DOI Web Site 参考文献39件
  • Kamada Haruhik
    Laboratory of Pharmaceutical Proteomics (LPP) National Institute of Biomedical Innovation (NIBIO)
  • Shibata Hiroko
    Laboratory of Pharmaceutical Proteomics (LPP) National Institute of Biomedical Innovation (NIBIO)
  • Tsutsumi Yasuo
    Laboratory of Pharmaceutical Proteomics (LPP) National Institute of Biomedical Innovation (NIBIO)

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説明

We have generated the first TNFR1-selective antagonistic TNF mutant based on structural human TNF variants using our phage display technology. This TNF mutant did not activate TNFR1-mediated responses, although its affinity for TNFR1 was equivalent to human wild-type TNF (wtTNF). The TNF mutant neutralized wtTNF-induced TNFR1-mediated bioactivity without influencing TNFR2-mediated bioactivity. In hepatitis mouse models, the antagonistic TNF mutant significantly blocked liver injury caused by inflammation. These results indicate that antagonistic TNF mutants may be clinically useful for anti-TNF therapy and that phage display libraries of protein ligands can be used to select for receptor subtype-selective antagonists.

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