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

ABSTRACT: 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.

SUBMITTER: Goh AX 

PROVIDER: S-EPMC4011920 | biostudies-literature | 2014 May-Jun

REPOSITORIES: biostudies-literature