Title: A soluble 17 kDa tumour necrosis factor (TNF) mutein, TNF-SAM2, with membrane-bound TNF-like biological characteristics.
Abstract: Membrane-bound tumour necrosis factor (TNF) has a different binding affinity to two TNF receptors (TNFR1 and TNFR2) and shows different biological activities compared with TNF-alpha. We have developed a mutein, TNF-SAM2, which has modified TNF-alpha. It has higher tumour killing activity than TNF-alpha and fewer side effects.The difference between TNF-SAM2 and TNF-alpha was examined in view of the binding affinity to each TNF receptor, cytotoxicity and expression of genes using Colo205 cells.The KD value of TNF-alpha (2. 9x1-7 M) for TNFR1 was lower than TNF-SAM2 (6.9x10(-7) M). Cytotoxicity of TNF-SAM2 was significantly higher than for TNF-a. RNA of Colo205 cells stimulated with TNF-SAM2 indicated that 80 genes increased by a factor of 2 or more, and 69 genes decreased.TNF-SAM2 can induce different intracellular signal transduction in Colo205 cells compared with TNF-alpha. TNF-SAM2 may have characteristics of the membrane-bound form despite the fact that is in a soluble form.
Publication Year: 2007
Publication Date: 2007-01-02
Language: en
Type: article
Indexed In: ['pubmed']
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Cited By Count: 10
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