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

Abstract

The epidermal growth factor receptor (EGFR) is aberrantly activated in many human epithelial cancers. This report presents the preparation, purification, and the anti-cancer potency of an anti-EGFR affibody (ZEGFR 1907)-polyethylenimine (PEI)-polyIC complex (PPEA-polyplex). Surface plasmon resonance analysis showed that the ZEGFR 1907 affibody binds tightly to full-length sEGFR with an average equilibrium dissociation constant, KD, value of 6.74 nM. The PPEA-polyplex does not activate the EGFR kinase, but kills tumor cells expressing medium to high levels of EGFR. The PPEA-polyplex stimulates the release of chemotactic cytokines (e.g., GRO-, IFN-{gamma}-inducible protein-10) and promoted PBMC-mediated bystander killing of non-transfected tumor cells. The PPEA-polyplex inhibited the growth of human epidermoid vulval carcinoma (A431) xenografts growing in immunocompromised nude mice. PPEA-polyplexes have the potential to inhibit the growth of tumors in Triple-negative breast cancer (TNBC) patients and other cancers which over-express the EGFR.