Publikation

Induction of long-lasting cytokine effect by injection of IL-12 encoding plasmid DNA

Wissenschaftlicher Artikel/Review - 01.12.2000

Bereiche
PubMed
DOI

Zitation
Schultz J, Heinzerling L, Pavlovic J, Moelling K. Induction of long-lasting cytokine effect by injection of IL-12 encoding plasmid DNA. Cancer gene therapy 2000; 7:1557-65.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Cancer gene therapy 2000; 7
Veröffentlichungsdatum
01.12.2000
ISSN (Druck)
0929-1903
Seiten
1557-65
Kurzbeschreibung/Zielsetzung

We have recently demonstrated that DNA coding for both subunits of the murine IL-12 heterodimer exhibits a strong antimetastatic effect against B16-melanoma in C57BL/6 mice and after intratumoral injection tumor regression. Here we show that the antimetastatic effect can be detected when the DNA is injected intramuscularly 30 days before tumor cell challenge. A long-term IL-12 expression was measured for up to 50 days in the serum with a peak at day 20 amounting to about 10 ng/mL in C57BL/6 mice. CpG oligodeoxynucleotides also induce IL-12 expression, however, only for a few hours. IL-12 DNA administration induces long-lasting systemic IFN -gamma production, whereas IL-4 and TNF-alpha levels remained undetectable. NK cell-depleted mice showed a strong but reduced expression of murine IL-12. Expression of DNA encoding human instead of murine IL-12 resulted in a significantly lower and transient expression, indicating that not plasmid-derived IL-12 production alone but the immune system of the host contributes to the long- lasting antimetastatic effect. It may be attributable to an autocrine feedback mechanism maintaining murine IL- 12 expression, whereby several cell populations including NK cells are involved.