GB12-09, a bispecific antibody targeting IL4Rα and IL31Rα for atopic dermatitis therapy.
Antib Ther
; 7(1): 77-87, 2024 Jan.
Article
en En
| MEDLINE
| ID: mdl-38371956
ABSTRACT
Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by dysregulated immune responses. The key mediators of AD pathogenesis are T helper 2 (TH2) cells and TH2 cytokines. Targeting interleukin 4 (IL4), IL13 or IL31 has become a pivotal focus in both research and clinical treatments for AD. However, the need remains pressing for the development of a more effective and safer therapy, as the current approaches often yield low response rates and adverse effects. In response to this challenge, we have engineered a immunoglobulin G-single-chain fragment variable (scFv) format bispecific antibody (Ab) designed to concurrently target IL4R and IL31R. Our innovative design involved sequence optimization of VL-VH and the introduction of disulfide bond (VH44-VL100) within the IL31Rα Ab scFv region to stabilize the scFv structure. Our bispecific Ab efficiently inhibited the IL4/IL13/IL31 signaling pathways in vitro and reduced serum immunoglobulin E and IL31 levels in vivo. Consequently, this intervention led to improved inflammation profiles and notable amelioration of AD symptoms. This research highlighted a novel approach to AD therapy by employing bispecific Ab targeting IL4Rα and IL31Rα with potent efficacy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Antib Ther
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos