PEGylated Recombinant Human Tumor Necrosis Factor Alpha: Pharmacokinetics and Anti-tumor Effects

Abstract

The aim of the present work was to investigate and assess the merit of PEGylated recombinant human tumor necrosis factor-α (rHuTNF-α) following our previous work. The rHuTNF-α was modified using activated polyethylene glycol (PEG), N-succinimidyl succinnate monomethoxy polyethylene glycol (SS-PEG). The pharmacokinetics and anti-tumor effect were investigated. The experimental results showed that PEGylated rHuTNF-α could obviously alter in vivo behavioral characteristics of rHuTNF-α. Among the synthesized PEG-rHuTNF-αs with different PEG molecules, PEG₂₀₀₀₀-rHuTNF-α demonstrated the longest circulating half-life (24.8 h) which was about 50 times longer than that of rHuTNF-α (28.8 min). In addition, there was much more PEG₂₀₀₀₀-rHuTNF-α distributed into tumor tissues than other PEG-rHuTNF-αs or rHuTNF-α with time, and PEG₂₀₀₀₀-rHuTNF-α also showed the highest anti-tumor potency. These results indicated that PEG₂₀₀₀₀-rHuTNF-α was a useful long circulating molecule with selective localization in tumor tissues and enhanced anti-tumor activity of rHuTNF-α.