A novel single domain bispecific antibody targeting VEGF and TNF-α ameliorates rheumatoid arthritis.

Anti-TNF-α therapy fails in 30% of patients, where TNF-α may not be the key causative factor in these patients. We developed a bispecific single-domain antibody block TNF-α and VEGF (V5-3).The experiments showed that V5-3 effectively activated proliferation and migration of RA-FLS and HUVEC, tube-forming role of HUVEC, and expression of inflammatory factors in vitro. Besides, the experiments indicated that the anti-RA activity of V5-3 was superior to Anbainuo in vivo. Application of V5-3 reduced the expression of inflammatory factors, extent of synovial inflammation and angiogenesis and attenuated the severity of autoimmune arthritis in collagen-induced arthritis (CIA) mice. Mechanistically, V5-3 suppressed p65, AKT and VEGFR2 phosphorylation, as well as production of TNF-α and VEGF in joint tissues. These results demonstrated that V5-3 displayed a superior effect of anti-RA, may be a new therapy to overcome the limitations of anti-TNF-α monoclonal antibody. Copyright © 2023 Elsevier B.V. All rights reserved.

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Nanwen Zhang, Ningning Zheng, Dunxiong Luo, Juan Lin, Duoduo Lin, Yongkang Lu, Weipeng Lai, Yize Bian, He Wang, Jian Ye, Juhua Yang, Jiaan Liu, Wenzhong Que, Xiaole Chen. A novel single domain bispecific antibody targeting VEGF and TNF-α ameliorates rheumatoid arthritis. International immunopharmacology. 2024 Jan 05;126:111240

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PMID: 37992444

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