title: 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.affiliation: Singapore Immunology Network; Agency for Science; Technology and Research (A*STAR); Singapore.
authors.forename: Angeline X H
authors.initials: AX
authors.lastname: Goh
authors.affiliation: Singapore Immunology Network; Agency for Science; Technology and Research (A*STAR); Singapore.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Bertin-Maghit
authors.affiliation: Singapore Immunology Network; Agency for Science; Technology and Research (A*STAR); Singapore.
authors.forename: Siok
authors.initials: S
authors.lastname: Ping Yeo
authors.affiliation: Singapore Immunology Network; Agency for Science; Technology and Research (A*STAR); Singapore.
authors.forename: Adrian W S
authors.initials: AW
authors.lastname: Ho
authors.affiliation: Singapore Immunology Network; Agency for Science; Technology and Research (A*STAR); Singapore.
authors.forename: Heidi
authors.initials: H
authors.lastname: Derks
authors.affiliation: Singapore Immunology Network; Agency for Science; Technology and Research (A*STAR); Singapore.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mortellaro
authors.affiliation: Singapore Immunology Network; Agency for Science; Technology and Research (A*STAR); Singapore.
authors.forename: Cheng-I
authors.initials: CI
authors.lastname: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D000915:Antibody Affinity; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy; D003429:Cross Reactions; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000276:immunology*; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy; D019151:Peptide Library; D010538:Peritonitis / Q000276:immunology / Q000628:therapy; D015202:Protein Engineering
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000939:Epitopes; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D019151:Peptide Library; C541220:canakinumab
keywords: animal models; antibody; drug discovery; immunotherapy; interleukin 1