EGFR-targeted affibody-polyIC polyplex kills EGFR-overexpressing cancer cells without activating the EGFR

Area of Science:

• Oncology
• Biotechnology
• Immunology

Background:

• Aberrant activation of the epidermal growth factor receptor (EGFR) is a common driver in numerous human epithelial cancers.
• Targeting EGFR is a validated strategy in cancer therapy, but novel delivery systems are needed.

Purpose of the Study:

• To prepare and characterize an anti-EGFR affibody-polyethylenimine-polyIC complex (PPEA-polyplex).
• To evaluate the in vitro and in vivo anti-cancer potency of the PPEA-polyplex against EGFR-overexpressing tumors.

Main Methods:

• Surface plasmon resonance was used to determine the binding affinity of the affibody to soluble EGFR (sEGFR).
• In vitro assays assessed the PPEA-polyplex's ability to kill tumor cells and stimulate cytokine release.
• In vivo studies evaluated the PPEA-polyplex's efficacy in inhibiting tumor xenograft growth in mice.

Main Results:

• The anti-EGFR affibody demonstrated high-affinity binding to sEGFR (KD = 6.74 nM).
• The PPEA-polyplex effectively killed EGFR-expressing tumor cells without activating EGFR kinase.
• The complex stimulated chemotactic cytokine release and promoted immune cell-mediated bystander killing, while also inhibiting tumor xenograft growth in vivo.

Conclusions:

• The PPEA-polyplex is a promising therapeutic agent for cancers with EGFR overexpression.
• This novel complex exhibits potent anti-tumor activity through direct cell killing and immune system activation.
• Further development of PPEA-polyplexes could lead to new treatments for cancers like colon and breast cancer.