A fully human monoclonal antibody with novel binding epitope and excellent neutralizing activity to multiple human IFN-a subtypes:A candidate therapy for systemic lupus erythematosus
Systemic lupus erythematosus(SLE)is a chronic,heterogeneous autoimmune disease short of effective therapeutic agents.A multitude of studies of SLE in the last decade have accentuated a central role of the interferon alpha(IFN-α)pathway in SLE pathogenesis.We report here a candidate therapeutic neutralizing antibody,AIA22,with a different binding epitope and discrepant neutralizing profile from the anti-multiple IFN-α subtype antibodies currently in clinical trials.AIA22 specifically interacts with multiple IFN-α subtypes,binds to the type Ⅰ IFN receptor 2(IFNAR2)recognition region of IFN-α(considered a novel antigen epitope),and effectively neutralizes the activity of almost all of the IFN-α subtypes(with the exception of IFN-α7)both in vitro and in vivo.Concurrently,structural modeling and computational design yielded a mutational antibody of AIA22,AlAmut,which exhibited substantially improved neutralizing activity to multiple IFN-α subtypes.
antigen epitope computational design interferon alpha monoclonal antibody neutralizing activity systemic lupus erythematosus
Peng Du Lei Xu Weiyi Qiu Dadi Zeng Junjie Yue Shuang Wang Peitang Huang Zhiwei Sun
Beijing Institute of Biotechnology;Beijing,China Beijing Institute of Biotechnology;Beijing,China;School of Life Science;Anhui University;Hefei,Anhui
国内会议
大连
英文
20-32
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）