TNF alpha Variant, Tumor Necrosis Factor-alpha Variant, human: The clinical use of the potent antitumor activity of TNF-αhas 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 murine TNF-R55 but not to the murine TNF-R75, exhibits retained antitumor activity and reduced systemic toxicity in mice compared with murine TNF-α, which binds to both murine 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., UnitProt ID: P01375