Administration of multiple cytokine genes with anti-tumor activity inhibits both tumor incidence and tumor growth

The finding of reporter gene expression in muscle cells after intramuscular injection of a reporter gene containing DNA has suggested that injection o f a certain gene in its naked form could induce an expression of the inject ed gene. The result proposed the concept, namely DNA or genetic vaccine tec hnology, that injection of an antigen gene could induce a specific immune r esponse against the antigen. Although the concept was initially applied to vaccination technology, the result also means that administration of cytoki ne genes with anti-tumor activity could exert their functions when they are applied as a naked form of DNA. To test the possibility, plasmid vector co ntaining granulocyte macrophage-colony stimulation factor (GM-CSF) and inte rleukin-12 (IL-12) genes, which are known as one of the most potent anti-tu mor cytokines, were constructed and injected into mice together with syngen eic tumor cells. When the cytokine gene containing plasmid was injected on the same day of tumor cell injection, a tumor mass developed in 4 out of 5 mice rested. Even among the 4 mice, the tumor mass of a mouse disappeared 2 weeks after tumor development. In addition, tumor generation was significa ntly delayed in cytokine gene injected mice and the average tumor size was about 51.5% that of vector control injected mice. These results suggested t hat tumor treatment through the injection of multiple cytokine genes with p otent anti-rumor activity significantly inhibits tumor development and grow th, and that the method could be considered as one of the tools for efficie nt tumor treatment.