J. Tan et al., INJECTION OF COMPLEMENTARY-DNA ENCODING INTERLEUKIN-12 INHIBITS TUMORESTABLISHMENT AT A DISTANT SITE IN A MURINE RENAL-CARCINOMA MODEL, Cancer research, 56(15), 1996, pp. 3399-3403
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.