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

Pettikiriarachchi, A; Ugolev, Y; Birkinshaw, R; Wardak, A; Faux, MC; Adams, TE; Joubran, S; Shir, A; Edinger, N; Zigler, M; Levitzki, A; Burgess, AW

Author(s): Pettikiriarachchi, A; Ugolev, Y; Birkinshaw, R; Wardak, A; Faux, MC; Adams, TE; Joubran, S; Shir, A; Edinger, N; Zigler, M; Levitzki, A; Burgess, AW;
Details: Publication Year 2026,Volume 21,Issue #5,Page e0334584
Journal Title: PloS One
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. As expected 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-α, IFN-γ-inducible protein-10) and promoted PBMC-mediated bystander killing of non-treated tumor cells. The PPEA-polyplex also inhibited the growth of human epidermoid vulval carcinoma (A431) xenografts growing in immunocompromised nude mice. Both the in vitro and in vivo results indicate that PPEA-polyplexes have the potential to inhibit the growth of tumors which over-express the EGFR, including colon and breast cancer cells.
Publisher: PLOS
Keywords: *ErbB Receptors/metabolism; Humans; Animals; Mice; Cell Line, Tumor; Xenograft Model Antitumor Assays; Mice, Nude; *Recombinant Fusion Proteins/pharmacology/chemistry/metabolism; Female; *Polyethyleneimine/chemistry
Research Division(s): Personalised Oncology; Structural Biology
PubMed ID: 42085373
Publisher's Version: https://doi.org/10.1371/journal.pone.0334584
Open Access at Publisher's Site: https://doi.org/10.1371/journal.pone.0334584
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-05-07 08:23:26

Last Modified: 2026-05-07 08:25:05