A fully human monoclonal antibody with novel binding epitope and excellent neutralizing activity to multiple human IFN-alpha subtypes: A candidate therapy for systemic lupus erythematosus

作者：Du Peng; Xu Lei; Qiu Weiyi; Zeng Dadi; Yue Junjie; Wang Shuang^*; Huang Peitang; Sun Zhiwei

来源：mAbs, 2015, 7(5): 969-980.

DOI：10.1080/19420862.2015.1055443

• interferon alpha
• systemic lupus erythematosus
• neutralizing activity
• monoclonal antibody
• computational design
• antigen epitope

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-alpha) 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-alpha subtype antibodies currently in clinical trials. AIA22 specifically interacts with multiple IFN-alpha subtypes, binds to the type I IFN receptor 2 (IFNAR2) recognition region of IFN-alpha (considered a novel antigen epitope), and effectively neutralizes the activity of almost all of the IFN-alpha subtypes (with the exception of IFN-alpha 7) both in vitro and in vivo. Concurrently, structural modeling and computational design yielded a mutational antibody of AIA22, AIAmut, which exhibited substantially improved neutralizing activity to multiple IFN-alpha subtypes.

• 出版日期2015-9-3
• 单位安徽大学