@misc{9235866,
  abstract     = {{Conventional monoclonal antibodies that function via occupancy-based inhibition often fall short due to drug resistance and non-enzymatic scaffolding functions that persist despite successful inhibition of the target protein. Antibody-based proteolysis targeting chimeras (AbTACs) utilize a novel event-driven modality allowing for specific degradation of the target protein. This study investigated the construction and characterization of bispecific tandem-single-chain fragment variable (tandem-scFv) AbTACs, designed to bind the oncogenic driver protein epidermal growth factor receptor (EGFR) and the membrane-bound E3 ubiquitin ligase ring finger protein 43 (RNF43). A panel of phage display-derived antibody clones was characterized through parallel ELISA and surface plasmon resonance epitope binning against reference antibodies. Two distinct EGFR-binding Fabs were identified that bind different epitopes on EGFR. These, along with an RNF43-binding Fab were converted to scFv format and also engineered to form bispecific tandem-scFvs. The effect of orientation when constructing tandem-scFvs was investigated in terms of binding affinity and expression yields. Format comparisons between the tandem-scFvs, Fabs, and scFvs were also conducted revealing insightful trends. Ultimately, this work establishes a valuable framework for the design and optimization of compact tandem-scFv degraders.}},
  author       = {{Úlfarsson, Magnús Gauti}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Construction and characterization of antibody fragment-based PROTACs engaging EGFR and RNF43}},
  year         = {{2026}},
}