PEGylated recombinant human tumor necrosis factor alpha: Pharmacokinetics and anti-tumor effects

The aim of the present work was to investigate and assess the merit of PEGy lated recombinant human tumor necrosis factor-a (rHuTNF-alpha) following ou r previous work. The rHuTNF-a was modified using activated polyethylene gly col (PEG), N-succinimidyl succinnate monomethoxy polyethylene glycol (SS-PE G), The pharmacokinetics and anti-tumor effect vr ere investigated. The exp erimental results showed that PEGylated rHuTNF-alpha could obviously alter in vivo behavioral characteristics of rHuTNF-alpha. Among the synthesized P EG-rHuTNF-alphas with different PEG molecules, PEG(20000)-rHuTNF-alpha demo nstrated the longest circulating half-life (24.8 h) which was about 50 time s longer than that of rHuTNF-alpha (28.8 min). In addition, there was much mure PEG(20000)-rHuTNF-alpha distributed into tumor tissues than other PEG- rHuTNF-alphas or rHuTNF-alpha with time, and PEG(20000)-rHuTNF-alpha also s howed the highest anti-tumor potency. These results indicated that PEG20000 -rHuTNF-alpha was a useful long circulating molecule with selective localiz ation in tumor tissues and enhanced anti-tumor activity of rHuTNF-alpha.