A novel class of anti-IL-12p40 antibodies: potent neutralization via inhibition of IL-12-IL-12Rß2 and IL-23-IL-23R.
MAbs
; 2(5): 539-49, 2010.
Article
en En
| MEDLINE
| ID: mdl-20724822
ABSTRACT
While current therapeutic antibodies bind to IL-12 and IL-23 and inhibit their binding to IL-12Rß1, we describe a novel antibody, termed 6F6, that binds to IL-12 and IL-23 and inhibits the interaction of IL-12 and IL-23 with their cognate signalling receptors IL-12Rß2 and IL23R. This antibody does not affect the natural inhibition of the IL-12/23 pathway by the antagonists monomeric IL-12p40 and IL-12p80, which suggests that a dual antagonist system is possible. We have mapped the epitope of 6F6 to domain 3 of the p40 chain common to IL-12 and IL-23 and demonstrate that an antibody bound to this epitope is sufficient to inhibit engagement of the signalling receptors. Antibodies with this unique mechanism of inhibition are potent inhibitors of IL-12 induced IFN-γ production and IL-23 induced IL-17 production in vitro, and in an in vivo model of psoriasis, treatment with a humanized variant of this antibody, h6F6, reduced the inflammatory response, resulting in decreased epidermal hyperplasia. We believe that this new class of IL-12/23 neutralising antibodies has the potential to provide improved potency and efficacy as anti-inflammatory agents, particularly in diseases characterized by an overproduction of IL-12.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Proteínas Recombinantes
/
Subunidad p40 de la Interleucina-12
/
Anticuerpos Monoclonales
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
MAbs
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2010
Tipo del documento:
Article