GB12–09, a bispecific antibody targeting IL4Rα and IL31Rα for atopic dermatitis therapy

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 an IgG-scFv (Immunoglobulin G—single-chain Fragment variable) format bispecific antibody 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 antibody scFv region to stabilize the scFv structure. Our bispecific antibody efficiently inhibited the IL4/IL13/IL31 signaling pathways in vitro and reduced serum Immunoglobulin E (IgE) 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 antibody targeting IL4Rα and IL31Rα with potent efficacy.