Injection of complementary DNA encoding interleukin-12 inhibits tumor establishment at a distant site in a murine renal carcinoma model.
Interleukin (IL-12) protein has been shown to elicit diverse immunological responses and potent antitumor activity. We demonstrate here that intradermal injection of IL-12 cDNA induces systemic biological effects 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 increase 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 growth was reduced in mice that received IL-12 cDNA, compared to mice given injections of plasmid vector alone. A number of the mice receiving IL-12 cDNA injections remained tumor free months after tumor challenge. In contrast to mice receiving recombinant IL-12 protein, no splenomegaly was detected when natural killer activity was significantly induced in mice receiving injections of IL-12 cDNA. Because purified plasmid DNA is more economical to prepare and has a longer shelf-life than recombinant 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-effective alternative to IL-12 protein therapy in some clinical or experimental therapeutic applications.
Tan
J
J
Immunology Program, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
Newton
C A
CA
Djeu
J Y
JY
Gutsch
D E
DE
Chang
A E
AE
Yang
N S
NS
Klein
T W
TW
Hua
Y
Y
D000818:Animals; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002455:Cell Division / Q000502:physiology; D018076:DNA, Complementary / Q000008:administration & dosage* / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007694:Killer Cells, Natural / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma