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MAbs. 2014 May-Jun;6(3):765-73. doi: 10.4161/mabs.28614. Epub 2014 Mar 26.

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

Author information

1
Singapore Immunology Network; Agency for Science; Technology and Research (A*STAR); Singapore.

Abstract

The pro-inflammatory cytokine interleukin (IL)-1β is a clinical target in many conditions involving dysregulation of the immune system; therapeutics that block IL-1β 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-1β 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-1β compared with its parent antibody. This anti-human IL-1β IgG also cross-reacts with mouse and monkey IL-1β, hence facilitating preclinical development. In a number of mouse models, this antibody efficiently reduced or abolished signs of disease associated with IL-1β 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-1β monoclonal antibody is a promising therapeutic candidate and a potential alternative to the current therapeutic arsenal.

KEYWORDS:

animal models; antibody; drug discovery; immunotherapy; interleukin 1

PMID:
24671001
PMCID:
PMC4011920
DOI:
10.4161/mabs.28614
[Indexed for MEDLINE]
Free PMC Article

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