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**AN3025** is a humanized antagonistic monoclonal antibody targeting human tumor necrosis factor receptor 2 (TNFR2). Generated via rabbit immunization with the TNFR2 extracellular domain followed by CDR grafting for humanization, it binds with sub-nanomolar affinity to human and cynomolgus TNFR2 but not mouse or rat orthologs. AN3025 competitively inhibits TNFα binding to TNFR2, blocking signaling that promotes regulatory T cell (Treg) survival and function, thereby reducing Treg populations in the tumor microenvironment, enhancing CD4+ and CD8+ T effector cell proliferation and IFNγ production, and driving potent anti-tumor efficacy in preclinical models such as MC38 colon cancer and B16F10 melanoma in humanized TNFR2 mice. It shows comparable activity to anti-PD-1 as monotherapy and superior synergy in combination, with development led by Adlai Nortye (licensed to Biotime for Greater China).
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