Targeted cancer treatment using a novel EGFR-specific Fc-fusion peptide based on GE11 peptide

Abstract

Fc-fusion peptides, also known as peptibodies, are a promising new category of targeted therapeutics that offer alternatives to monoclonal antibodies (mAbs) for cancer treatment. This study focuses on an Fc-fusion peptide consisting of the Fc region of IgG1 and an epidermal growth factor receptor (EGFR)-targeting peptide, GE11, which was identified using the phage display method and demonstrated high affinity for the receptor. The fusion peptide (FcIgG-GE11) was successfully expressed in Escherichia coli and purified using ion-exchange chromatography. Flow cytometry confirmed its specific binding to EGFR. Like Cetuximab, the FcIgG-GE11 peptibody exhibited effective, dose- and time-dependent growth inhibition of EGFR-overexpressing cancer cell lines. Additionally, the results showed that the FcIgG-GE11 peptibody induced cell death or cycle arrest in certain cancer cell lines, with varying responses depending on the cancer type. The results of In-Cell ELISA when comparing the effects of the FcIgG-GE11 peptibody to Cetuximab on Tyr 1173 phosphorylation were similar. In addition, the relative potency of the FcIgG-GE11 peptibody compared to Cetuximab was assessed using the MTT results by Slope Ratio Analysis. These findings suggest that FcIgG-GE11 peptibody can provide a specific and efficient tool for both targeting and treating cancer cells.