Recombinant Human TNF-alpha/TNFA Protein High Active Mutant Protein

This product is provided as lyophilized powder which is shipped with ice packs.

15-17 kDa

Tumor Necrosis Factor-alpha (TNF-alpha) is secreted by macrophages; monocytes; neutrophils; T-cells; and NK-cells following stimulation by bacterial LPS. Cells expressing CD4 secrete TNF-alpha while cells that express CD8 secrete little or no TNF-alpha. Synthesis of TNF-alpha can be induced by many different stimuli including interferons; IL2; and GM-CSF. The clinical use of the potent anti-tumor activity of TNF-alpha has been limited by the proinflammatory side effects such as fever; dose-limiting hypotension; hepatotoxicity; intravascular thrombosis; and hemorrhage. Designing clinically applicable TNF-alpha mutants with low systemic toxicity has been of intense pharmacological interest. Human TNF-alpha that binds to murine TNF-R55 but not murine TNF-R7; exhibits retained anti-tumor activity and reduced systemic toxicity in mice compared with murine TNF-alpha; which binds to both murine TNF receptors. Based on these results; many TNF-alpha mutants that selectively bind to TNF-R55 have been designed. These mutants displayed cytotoxic activities on tumor cell lines in vitro and have exhibited lower systemic toxicity in vivo. Recombinant Human TNF-alpha High Active Mutant differs from the wild-type by amino acid subsitution of amino acids 1-7 with Arg8; Lys9; Arg10 and Phe157. This mutant form has been shown to have increased activity with less inflammatory side effects in vivo.

Please refer to the printed manual for detailed information.

Measured in a cytotoxicity assay using L?929 mouse fibroblast cells in the presence of the metabolic inhibitor actinomycin D. The ED50 for this effect is 1.48 pg/ml.