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Biparatopic targeting of IL-23 enables dual-epitope engagement and enhanced neutralization potency - PubMed

4 hours ago
  • #biparatopic-antibodies
  • #IL-23-neutralization
  • #antibody-engineering
  • Engineered biparatopic antibodies (bpAbs) targeting human IL-23 by combining variable regions of ustekinumab and guselkumab into IgG-like and Fab-IgG formats.
  • BpAbs demonstrated picomolar affinities and avidity-driven affinity enhancements, with dual-epitope engagement confirmed via SPR bridging assay.
  • Mass photometry showed in trans immune complex formation and stoichiometry-dependent multimerization across bpAb formats.
  • Functional neutralization assays and a mechanistic model validated enhanced potency, equivalent to equimolar antibody mixtures, for soluble cytokine targeting.