Structure-based Development of Human Interleukin-1β-Specific Antibody That Simultaneously Inhibits Binding to Both IL-1RI and IL-1RAcP

IgG26AW antibody was optimized from the original IgG26 antibody selected from human phage-display library. Based on the crystal structure of the Fab fragment of IgG26 (termed 26-Fab) in complex with IL-1β, we found that the antibody IgG26 binds to the IL-1β epitope, which is occupied by the interaction domains of IL-1RI and IL-1RAcP simultaneously. By using the SPR experiments, we proved that the IL-1β bound with IgG26AW abolished the binding of IL-1RI and IL-1RAcP. In vivo IL-1β neutralization assay and experiments using two xenograft mouse tumor models were also performed to verify the biological inhibitory effect of IgG26AW. We conclude that IgG26AW inhibits IL-1β biological activity by preventing the assembly of the IL-1β/IL-1RI/IL-1RAcP ternary complex. Therefore, IgG26AW is a new IL-1β blocker which has potential to be developed into therapeutic drugs.