Antitumor effect of systemic administration of novel recombinant tumor necrosis factor (rTNF-S) with less toxicity than conventional rTNF-alpha in vivo.
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.
Gatanaga
T
T
Biotechnology Research Center, Teikyo University, Kanagawa, Japan.
Noguchi
K
K
Tanabe
Y
Y
Inagawa
H
H
Soma
G
G
Mizuno
D
D
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
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha