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

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.

• Authors: Angeline X H Goh, Sebastien Bertin-Maghit, Siok Ping Yeo, Adrian W S Ho, Heidi Derks, Alessandra Mortellaro, Cheng-I Wang
• Journal: mAbs (MAbs) 2014 May-Jun Vol. 6 Issue 3 Pg. 765-73 ISSN: 1942-0870 [Electronic] United States
• PMID: 24671001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antibodies, Neutralizing
• Epitopes
• Immunoglobulin G
• Interleukin-1beta
• Peptide Library
• canakinumab

Topics

• Animals
• Antibodies, Monoclonal (genetics, immunology, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antibodies, Neutralizing (genetics, immunology, therapeutic use)
• Antibody Affinity
• Arthritis, Experimental (immunology, therapy)
• Cross Reactions
• Disease Models, Animal
• Epitopes (immunology)
• Female
• Humans
• Immunoglobulin G (genetics, immunology, therapeutic use)
• Inflammation (immunology, therapy)
• Interleukin-1beta (antagonists & inhibitors, immunology)
• Macaca mulatta
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Inbred NOD
• Mice, SCID
• Multiple Myeloma (immunology, therapy)
• Peptide Library
• Peritonitis (immunology, therapy)
• Protein Engineering