Development of an anti-EREG therapeutic antibody for sclerotic GVHD and scleroderma
Newton NM, Agrawal K, Odell AV, et al. Sclerotic GVHD and Scleroderma Share Dysregulated Gene Expression That Is Ameliorated by EREG Therapeutic Antibody. Blood. 2025; (doi: 10.1182/blood.2025029836).
Researchers have developed a neutralizing antibody with the potential to improve quality-of-life and survival outcomes in patients with immune-driven fibrotic skin conditions. EREG, a DC3 dendritic cell-derived EGFR ligand, is expressed on the skin in cases of scleroderma/systemic sclerosis, sclerotic chronic graft-versus-host-disease, and localized scleroderma. In each disease setting, EREG promotes production of TNC, a pro-inflammatory extracellular glycoprotein that acts as an endogenous TLR4 ligand, which stimulates expression of two TLR4 target genes: CCL2 and IL6. When treated with the anti-EREG therapeutic antibody, explants of sclerotic skin demonstrated a reduction in inflammatory and fibrosis biomarkers associated with the EGFR-TNC-TLR4 signaling axis. The antifibrotic properties observed in vivo are promising for a set of diseases lacking effective therapeutic alternatives, according to investigators, who believe their antibody is "highly developable."