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4B1 is a high-affinity monoclonal antibody targeting the CD3ε subunit of the T-cell receptor (TCR)-CD3 complex. Developed by researchers at the Harbin Institute of Technology, Westlake University, and Harbin Blood Center, 4B1 binds to CD3ε with a strict 1:1 stoichiometry, unlike the classic anti-CD3 antibody OKT3 which binds with a 2:1 stoichiometry. This unique binding mode induces mild TCR clustering and triggers a biased, finely tuned T-cell activation. Consequently, 4B1-based bispecific antibodies demonstrate potent tumor-killing activity while significantly reducing the release of inflammatory cytokines, thereby uncoupling T-cell cytotoxicity from cytokine release syndrome (CRS). It is being investigated as a safer structural blueprint for next-generation T-cell engagers in cancer immunotherapy.
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