INJECTION OF COMPLEMENTARY-DNA ENCODING INTERLEUKIN-12 INHIBITS TUMORESTABLISHMENT AT A DISTANT SITE IN A MURINE RENAL-CARCINOMA MODEL

Interleukin (IL-12) protein has been shown to elicit diverse immunolog ical responses and potent antitumor activity. We demonstrate here that intradermal injection of IL-12 cDNA induces systemic biological effec ts characteristic of the cytokine in vivo. Intradermal injection of IL -12 cDNA resulted in local expression of IL-12 mRNA, which correlated with a 10-fold increase in natural killer activity and a 3-4-fold incr ease in anti-CD3-induced IFN-gamma production in cultured splenocytes, Furthermore, when challenged with Renca tumor cells at a distant site , the day of tumor emergence was significantly delayed, and tumor grow th was reduced in mice that received IL-12 cDNA, compared to mice give n injections of plasmid vector alone. A number of the mice receiving I L-12 cDNA injections remained tumor free months after tumor challenge. In contrast to mice receiving recombinant IL-12 protein, no splenomeg aly was detected when natural killer activity was significantly induce d in mice receiving injections of IL-12 cDNA. Because purified plasmid DNA is more economical to prepare and has a longer shelf-life than re combinant proteins, and intradermal administration of cDNA encoding IL -12 did not cause splenomegaly, our findings suggest that the in vivo injection of cDNA encoding IL-12 may be a less toxic and more cost-eff ective alternative to IL-12 protein therapy in some clinical or experi mental therapeutic applications.