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.