A soluble 17 kDa tumour necrosis factor (TNF) mutein, TNF-SAM2, with membrane-bound TNF-like biological characteristics
Yoshida, A.; Kohchi, C.; Inagawa, H.; Nishizawa, T.; Hori, H.; Soma, G.-I.
Anticancer Research 26(6a): 4003-4007
2006
ISSN/ISBN: 0250-7005 PMID: 17195449 Document Number: 601664
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.