원문정보
초록
영어
Tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) is an attractive anticancer therapeutic due to the tumor cell specificity. However its rapid inactivation, low stability and solubility, and severe hepatotoxicity on systemic delivery have been considered as critical obstacles for clinical applications. Chemical PEGylation is a known means to increase stability and to influence pharmacokinetic properties of a protein therapeutic.
In this study, we applied the N-terminal specific PEGylation technology on active trimeric TRAIL for enhanced pharmaceutical characteristics with improved tumor therapeutic efficacy. The PEG-TRAIL showed improved physiological stability and pharmacokinetic profile than unmodified TRAIL with minimal activity loss. The improved pharmacological characteristics resulted in the
enhanced therapeutic potentials on inoculated tumor animal models without detectable side effects. Furthermore, the in vivo tumor targeting capacity might offer the possibility of the PEG-TRAIL as new tumor target therapeutics.