2026-09-19 中国科学院（CAS）
＜関連情報＞
- https://english.cas.cn/newsroom/research-news/202609/t20260920_1200895.shtml
- https://www.cell.com/structure/abstract/S0969-2126(26)00259-5
喘息およびCOPD治療のためのインターロイキン-33中和剤QX007Nの構造的基盤 Structural basis of QX007N neutralizing interleukin-33 for asthma and COPD treatment
Qi Wang ∙ Huimin Ke ∙ Yiliang Wu ∙ … ∙ Tao Chen ∙ Wei Li ∙ Wei Feng
Structure Published:September 18, 2026
DOI:https://doi.org/10.1016/j.str.2026.08.012
Highlights
- QX007N is a humanized therapeutic antibody specifically targeting IL-33
- QX007N effectively inhibits the IL-33-mediated signaling pathway
- Crystal structures of QX007N-Fab and its complex with IL-33 were determined
- QX007N blocks IL-33/ST2/IL-1RAcP complex assembly by competing with ST2
Summary
Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is upregulated in various inflammatory and allergic diseases, including asthma and chronic obstructive pulmonary disease (COPD). In this study, we report the generation and functional characterization of QX007N, a humanized monoclonal antibody that specifically neutralizes IL-33. QX007N shows high neutralization activities against IL-33-mediated signaling. In B-hIL-33 humanized mice, QX007N significantly suppressed ovalbumin (OVA)-specific IgE levels in serum and attenuated acute allergic inflammation in lung cells. Crystal structures of the QX007N-Fab (2.62 Å) and its complex with IL-33 (2.60 Å) were determined. Structural comparison of the QX007N-Fab/IL-33 complex with published antibody/IL-33 complexes and the IL-33/suppression of tumorigenicity 2 (ST2) complex reveals that QX007N-Fab recognizes epitope 2 on IL-33 and sterically inhibits ST2 binding, thereby preventing assembly of the IL-33/ST2/IL-1RAcP signaling complex and downstream signal transduction. These findings establish QX007N as a promising therapeutic candidate for asthma and COPD.
