A novel recombinant tumor necrosis factor-alpha mutant with increased anti-tumor activity and lower toxicity

✍ Scribed by Satoshi Nakamura; Arata Kato; Tsukio Masegi; Masami Fukuoka; Kazuo Kitai; Hiroko Ogawa; Yataro Ichikawa; Masahiro Maeda; Naoki Watanabe; Yutaka Kohgo; Yoshiro Niitsu

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: French
• Weight: 500 KB
• Volume: 48
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910480519

✦ Synopsis

We prepared a novel recombinant tumor necrosis factor-u (TNF) mutant (mutant 471), in which 7 N-terminal aminoacids were deleted and ProsSer9Asp'0 was replaced by ArgLysArg, and compared its biological activity with that of wild-type recombinant TNF. Mutant 471 had a 7-fold higher anti-tumor activity against murine L-M cells in vitro, and a higher binding activity to TNF receptors on L-M cells, than wild-type TNF. Furthermore, mutant 471 showed a higher anti-tumor effect on murine Meth A-HM tumors transplanted into BALB/c mice, with complete regression of the tumors being observed in the animals. The possible cachectin activity of mutant 471 was almost the same as that of wild-type TNF. The acute lethal toxicity of mutant 471 in P-o-galactosamine-sensitized C3H/HeJ mice was 18 times lower than that of wild-type TNF. These results suggest that mutant 471 might be a more promising anti-cancer agent than wild-type TNF.