Development of an EGFR-targeted adenoviral E4orf4 protein nanoparticle for cancer therapy

초록

Early region 4 open reading frame 4 (E4orf4), a protein derived from human adenovirus, selectively induces non-canonical apoptosis in transformed cells by inhibiting multiple oncogenic signaling pathways. In this study, we designed an epidermal growth factor receptor (EGFR)-targeted E4orf4 fusion protein, termed rE94, by incorporating a repebody as the targeting domain. The rE94 protein was stably expressed in a soluble and particulate form using a bacterial expression system, exhibiting high specificity and binding affinity for EGFR, which is comparable to that of the parental anti-EGFR repebody (rEgH9). In vitro cell viability assays demonstrated that rE94 induces apoptosis in EGFR-overexpressing tumor cells in a receptor-dependent manner, while the parental repebody exhibited negligible cytotoxicity. These findings highlight the potential of rE94 as a targeted therapeutic for various tumors, offering an effective approach in precision oncology.

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