Improvement of cytotoxicity of tumor necrosis factor (TNF) by increase in basicity of its N-terminal region.
Two new recombinant TNFs (named rTNF-Scw1 and -Scw2) with higher basicity than conventional recombinant human TNF-alpha (rTNF-alpha) in the N-terminal region were constructed. Their sequences were constructed based on those of partially purified cytotoxic factors from the culture supernatant of acute monocytic leukemia cells THP-1, which unlike rTNF-alpha are cytotoxic to T24 bladder carcinoma cells in vitro. These new rTNF-Ss showed a broader cytotoxicity to tumor cells than rTNF-alpha. This increase in the basicity of the N-terminal region over that of conventional TNF significantly increased the cytotoxicity on tumor cells in vivo as well as in vitro.
Soma
G
G
Biotechnology Research Center, Teikyo University, Kanagawa, Japan.
Kitahara
N
N
Tsuji
Y
Y
Kato
M
M
Oshima
H
H
Gatanaga
T
T
Inagawa
H
H
Noguchi
K
K
Tanabe
Y
Y
Mizuno
D
D
D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D007739:L Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000633:toxicity*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000302:isolation & purification / Q000633:toxicity*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha