A novel human anti- interleukin-1∼ neutralizing monoclonal antibody showing in vivo efficacy

The pro-inflammatory cytokine interleukin (IL)-1 is a clinical target in many conditions involving dysregulation of the immune system; therapeutics that block IL-1 have been approved to treat diseases such as rheumatoid arthritis (RA), neonatal onset multisystem inflammatory diseases, cryopyrin-associated periodic syndromes, active systemic juvenile idiopathic arthritis. Here, we report the generation and engineering of a new fully human antibody that binds tightly to IL-1 with a neutralization potency more than 10 times higher than that of the marketed antibody canakinumab. After affinity maturation, the derived antibody shows a >30-fold increased affinity to human IL-1 compared with its parent antibody. This anti-human IL-1 IgG also cross-reacts with mouse and monkey IL-1, hence facilitating preclinical development. In a number of mouse models, this antibody efficiently reduced or abolished signs of disease associated with IL-1 pathology. Due to its high affinity for the cytokine and its potency both in vitro and in vivo, we propose that this novel fully human anti-IL-1 monoclonal antibody is a promising therapeutic candidate and a potential alternative to the current therapeutic arsenal.