title: Antitumor effect of systemic administration of novel recombinant tumor necrosis factor (rTNF-S) with less toxicity than conventional rTNF-alpha in vivo.
abstract: This study reported that acute toxicity (expressed as the LD50 value) of rTNF-SAM1 and rTNF-SAM2 which we constructed was considerably lower than that of rTNF-alpha (1). Following this finding, the antitumor effects of systemic administration of these novel recombinant tumor necrosis factors (TNF-S) (named rTNF-SAM1 and rTNF-SAM2) were examined in vivo on murine tumors (Meth A fibrosarcoma, MH134 hepatoma, and B16 melanoma). Both rTNF-SAM1 and rTNF-SAM2 could be administered systemically to tumor-bearing mice at doses up to 3 X 10(4) to 10(5) U. Growth of all tumors was significantly inhibited by systemic administration of rTNF-SAM1 or rTNF-SAM2 at a dose of greater than 3 X 10(4) U; at this dosage conventional rTNF-alpha could not be administered systemically to any of the mice strains due to its toxicity. These results confirm our previous finding that the rTNF-SAM group can be administered with safety at higher doses than rTNF-alpha, and revealed that these novel rTNF-S could be more promising antitumor drugs than rTNF-alpha in view of their lower toxicity compared with antitumor effect.
authors.affiliation: Biotechnology Research Center, Teikyo University, Kanagawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Gatanaga
authors.forename: K
authors.initials: K
authors.lastname: Noguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Tanabe
authors.forename: H
authors.initials: H
authors.lastname: Inagawa
authors.forename: G
authors.initials: G
authors.lastname: Soma
authors.forename: D
authors.initials: D
authors.lastname: Mizuno
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha