Immune modulation in cancer using DNA inoculation--antitumour effect of interleukin-12

DNA vaccines hold great promise for the prevention and therapy of infectious diseases and cancer. Furthermore, DNA has a high potential value not only for vaccination but also for therapy. Gene products which exhibit high potential biological potency, even at low levels of expression, are the most promising candidates. We have recently demonstrated that intramuscular injection of plasmid DNA coding for IL-12 abolishes the establishment of pulmonary metastases of 816F10 melanoma cells in a syngeneic mouse model. Based on these findings, we have evaluated the antitumour effect of IL-12 DNA therapy in a tumour model. Intramuscular injection of a murine IL-12-encoding DNA plasmid resulted in a pronounced reduction of tumour growth using preestablished syngeneic tumours in C57/BL6 mice. This antitumour effect correlated with a long-lasting expression of cytokines, which manifested itself as high levels of IL-12 in the serum 12 days after DNA treatment. The absence of significant toxic side effects could represent a significant advantage of IL-12 DNA therapy.