A novel human anti-interleukin-1ß neutralizing monoclonal antibody showing in vivo efficacy.
MAbs
; 6(3): 765-73, 2014.
Article
en En
| MEDLINE
| ID: mdl-24671001
ABSTRACT
The pro-inflammatory cytokine interleukin (IL)-1ß is a clinical target in many conditions involving dysregulation of the immune system; therapeutics that block IL-1ß 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-1ß 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-1ß compared with its parent antibody. This anti-human IL-1ß IgG also cross-reacts with mouse and monkey IL-1ß, hence facilitating preclinical development. In a number of mouse models, this antibody efficiently reduced or abolished signs of disease associated with IL-1ß 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-1ß monoclonal antibody is a promising therapeutic candidate and a potential alternative to the current therapeutic arsenal.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interleucina-1beta
/
Anticuerpos Neutralizantes
/
Anticuerpos Monoclonales
Idioma:
En
Revista:
MAbs
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2014
Tipo del documento:
Article