Improved antitumor activity and tumor targeting of NH2-terminal- specific PEGylated tumor necrosis factor-related apoptosis-inducing ligand

Su Young Chae, Tae Hyung Kim, Kyeongsoon Park, Cheng Hao Jin, Sohee Son, Seulki Lee, Yu Seok Youn, Kwangmeyung Kim, Dong Gyu Jo, Ick Chan Kwon, Xiaoyuan Chen, Kang Choon Lee

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)


Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered an attractive anticancer agent due to its tumor cell-specific cytotoxicity. However, its low stability, solubility, unexpected side effects, and weak pharmacokinetic profiles restrict its successful clinical application. To develop efficient TRAIL-based anticancer biotherapeutics, a new version of trimeric TRAIL was constructed by incorporating trimer-forming zipper sequences (HZ-TRAIL), and then NH2-terminal-specific PEGylation was done to produce PEGylated TRAIL (PEG-HZ-TRAIL). The biological, physicochemical, and pharmaceutical characteristics of PEG-HZ-TRAIL were then investigated using various in vitro and in vivo experiments, including a cell-based cytotoxicity test, a solubility test, pharmacokinetic analysis, and antitumor efficacy evaluations. Although slight activity loss occurred after PEGylation, PEG-HZ-TRAIL showed excellent tumor cell-specific cytotoxic effects via apoptotic pathways with negligible normal cell toxicity. The stability and pharmacokinetic problems of HZ-TRAIL were successfully overcome by PEGylation. Furthermore, in vivo antitumor tests revealed that PEG-HZ-TRAIL treatment enhanced therapeutic potentials compared with HZ-TRAIL in tumor xenograft animal models, and these enhancements were attributed to its better pharmacokinetic properties and tumor-targeting performance. These findings show that PEG-HZ-TRAIL administration provides an effective antitumor treatment, which exhibits superior tumor targeting and better inhibits tumor growth, and suggest that PEG-HZ-TRAIL should be considered a potential candidate for antitumor biotherapy.

Original languageEnglish
Pages (from-to)1719-1729
Number of pages11
JournalMolecular cancer therapeutics
Issue number6
Publication statusPublished - 2010 Jun

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Improved antitumor activity and tumor targeting of NH<sub>2</sub>-terminal- specific PEGylated tumor necrosis factor-related apoptosis-inducing ligand'. Together they form a unique fingerprint.

Cite this