Chemical Modification of Natural Human Tumor Necrosis Factor‐α with Polyethylene Glycol Increases Its Anti‐tumor Potency

Natural human tumor necrosis factor‐α (TNF‐α) was chemically modified with an active ester of monomethoxy polyethylene glycol (PEG). The molecular weight of PEG‐modified TNF‐a depended on the reaction time as well as the initial molar ratio of PEG to TNF‐α. The specific activity of modified TNF‐α was gradually reduced with increase in the degree of PEG‐modification, but the plasma half‐life of TNF‐α was increased by up to 40‐fold. Modified TNF‐α showed approximately 100 times greater anti‐tumor potency than unmodified TNF‐α. Covalent attachment of PEG to TNF‐α thus increased the bioavailability of TNF‐α, and may facilitate its potential therapeutic use.