Biological activities of novel recombinant tumor necrosis factor having N-terminal amino acid sequences derived from cytotoxic factors produced by THP-1 cells.
Eight species of novel recombinant tumor necrosis factor-S (rTNF-SAM group) were constructed in which N-terminal amino acid sequences were based on that of TNF-S from THP-1 cells with higher basicity than conventional rTNF-alpha. Two of this rTNF-SAM group, denoted as rTNF-SAM1 and rTNF-SAM2, showed more cytocidal activity on A549 lung carcinoma cells and G401 Wilm's tumor cells than did rTNF-alpha. In addition to these cell lines, rTNF-SAM1 revealed strong cytocidal activity on T24 bladder carcinoma cells, which are resistant to rTNF-alpha. Moreover, possible cachectin activity of rTNF-SAM2 seemed to be lower than that of conventional rTNF-alpha, suggesting that rTNF-SAM2 has less side effects. Actually, toxicity as expressed by LD50 value of rTNF-SAM2 as well as others of the rTNF-SAM group was significantly lower than that of conventional rTNF-alpha. Thus, newly constructed rTNF-SAM1 and rTNF-SAM2 should be more promising antitumor reagents for clinical use, since they were shown to be superior to conventional rTNF-alpha both in antitumor effect and in less side effects.
Soma
G
G
Biotechnology Research Center, Teikyo University, Kanagawa, Japan.
Tsuji
Y
Y
Tanabe
Y
Y
Noguchi
K
K
Kitahara-Tanabe
N
N
Gatanaga
T
T
Inagawa
H
H
Kawakami
M
M
Mizuno
D
D
D000595:Amino Acid Sequence; D008066:Lipolysis / Q000187:drug effects; D008071:Lipoprotein Lipase / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D009396:Wilms Tumor / Q000188:drug therapy*
D010446:Peptide Fragments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008071:Lipoprotein Lipase