Objective:To develop an agent that is more active against receptor bearing target cells without increasing the toxic effect on non target cells.Methods:By the use of molecular biology techniques,we designed and constructed a fusion protein 5′IL6 TNF △ by connecting the human interleukin 6 (hIL 6) gene and a human tumor necrosis factor α derivative (TNF △) gene through a synthetic linker sequence followed by subsequent expression in E.coli .Results:In cytotoxicity assay with myeloma cell line U266,the normal type of 5′IL6 TNF △ showed an antitumor activity 3 times higher than that of TNF △;and the antitumor activity of 5′IL6 TNF △ blocked by IL 6R was only 1/30 of that of normal type of 5′IL6 TNF △.Meanwhile,the 5′IL6 TNF △ blocked by anti TNF antibody did not show any cytotoxicity to U266 cells.In activity assay with L929 cells,the toxic effect of the fusion protein was found 1/22 of that of TNF △.Conclusion:The 5′IL6 TNF △ fusion protein might be a useful cytotoxic agent in cancer treatment.
