Toxicity testing of epidermal growth factor receptor-targeted hybrid peptide for preclinical study

Background: We previously reported that EGFR2R-lytic hybrid peptide was generated from the chemical conjugation of an epidermal growth factor receptor (EGFR) targeted peptide and a cell-killing lytic peptide. This peptide had effective cytotoxic and anti-tumor activities in vitro and in vivo against EGFR expressing cancers, suggesting it may be a novel candidate for a molecular-targeted anti-cancer drug. Methods: In this preclinical study, the toxicity of this hybrid peptide was examined in mice by monitoring body weight, performing clinical and biochemical examinations of blood samples, and observing histological changes. Results: No remarkable toxicity after intravenous injection of the hybrid peptide was observed up to a dose of 15 mg/kg, although a decrease in the alveolar space of the lung was identified from histological observations. Toxicity of the EGFR2R-lytic hybrid peptide in mice was also tested after oral administration. A significant change in body weight was not observed until a single dose of 300 mg/kg, but a decrease in body weight was observed at repeated doses of 75 or 150 mg/kg. However, the tendency for body weight increase was similar between the saline (control) and hybrid peptide groups after the completion of the administration period. In the case of oral administration, the dosage of the hybrid peptide could be increased to a significantly higher range compared with intravenous administration without serious toxicity. Conclusion: The results of this study should facilitate further preclinical studies on the EGFR2R-lytic hybrid peptide and its application in future cancer therapies.