Description
The clinical use of the potent antitumor activity of TNF-α has been limited by the proinflammatory side effects including fever, dose-limiting hypotension, hepatotoxicity, intravascular thrombosis, and hemorrhage. Designing clinically applicable TNF-αmutants with low systemic toxicity has been an intense pharmacological interest. Human TNF-α, which binds to the Mouse TNF-R55 but not to the Mouse TNF-R75, exhibits retained antitumor activity and reduced systemic toxicity in mice compared with Mouse TNF-α, which binds to both Mouse TNF receptors. Based on these results, many TNF-αmutants that selectively bind to TNF-R55 have been designed. These mutants displayed cytotoxic activities on tumor cell lines in vitro, and exhibited lower systemic toxicity in vivo