Release time：May 16, 2024
Mabwell (688062.SH), an innovation-driven biopharmaceutical company, presented the preclinical research findings of its self-developed anti-CXCR6 monoclonal antibody (R&D code: 2MW3311) at the 20th PEGS Boston - The Essential Protein and Antibody Engineering Summit, held from May 13-17, 2024.
Poster Presentation
Abstract title: 2MW3311: Combating autoimmune diseases by depleting pathogenic T cells via anti-CXCR6
Abstract code: A064
Auto-reactive T cells are central to the pathogenesis of many autoimmune diseases, persistently or periodically activated and expanded based on the specific disease conditions. However, indiscriminate T cell depletion in clincilal settings is limited due to increased adverse effects. Precise depletion of pathogenic T cells presents a promising treatment approach for autoimmune diseases.
2MW3311 is a humanized anti-CXCR6 monoclonal antibody developed by Mabwell. CXCR6, a member of CXC chemokine receptor family, predominantly expressed by a subset of T cells exhibiting characteristics of newly activated, clonally expanded, and tissue-resident properties. These CXCR6+ T cells are pivotal pathogenic cells in various autoimmune diseases. CXCL16, the sole ligand of CXCR6, is expressed by dendritic cells, monocytes, and macrophages. The expression level of CXCL16 is substantially up-regulated during inflammation. The CXCL16-CXCR6 chemotactic axis mediates the tissue migration and residence of CXCR6+ T cells, and subsequently contributes in the further activation and expansion of CXCR6+ T cells. CXCR6-CXCL16 axis plays important roles in the pathogenesis of many autoimmune diseases, such as MS, vitiligo, IBD, PSO, RA and AIH/NASH. Therefore, targeting CXCR6 offers a viable therapeutic strategy to precisely removing auto-reactive pathogenic T cells.
2MW3311 specifically binds to CXCR6 (human & cynomolgus) and has been modified by antibody engineering to optimize physicochemical properties and mouse/NHP pharmacokinetics. In various auto-immune disease models such as mouse EAE, CIA and GvHD, 2MW3311 demonstrated significant therapeutic effects by depleting CXCR6+ T cells. Moreover, multiple high-dose administrations of 2MW3311 displayed a favorable safety profile in NHP toxicology experiments. Currently in preclinical CMC development, 2MW3311 aims for clinical indications including multiple sclerosis, vitiligo, Crohn's disease, ulcerative colitis and primary bile acid cholangitis.
