We have evaluated whether i.p. murine ovarian
tumors could be treated with an
IL-2 plasmid
DNA complexed with the cationic
lipid, (+/-)-N-(2-hydroxyethyl)-N,N-dimethyl-2, 3-bis(tetradecyloxy)-1-propanaminium
bromide/
dioleoylphosphatidylethanolamine (
DMRIE/DOPE). Reporter gene studies were initially conducted in which mice bearing i.p. murine ovarian
teratocarcinoma (MOT) were injected i.p. with reporter gene plasmid
DNA (pDNA):
DMRIE/DOPE. Histochemical analyses revealed that transfection occurred primarily in the
tumor cells of the
ascites, with only a minority of other ascitic cells or surrounding tissues transfected.
IL-2 levels in the MOT
ascites were determined after i. p. injection of either
IL-2 pDNA:
DMRIE/DOPE or recombinant
IL-2 protein.
IL-2 was detected in
tumor ascites for up to 10 days after a single i.p. injection of
IL-2 pDNA:
DMRIE/DOPE, but was undetectable 24 h after a single i.p. injection of
IL-2 protein. In an antitumor efficacy study, MOT
tumor-bearing mice injected i.p. with
IL-2 pDNA:
DMRIE/DOPE on days 5, 8, and 11 after
tumor cell implant had a significant inhibition of
tumor ascites (p = 0.001) as well as a significant increase in survival (p = 0.008). A
cytokine profile of the MOT
tumor ascites revealed that mice treated with
IL-2 pDNA:
DMRIE/DOPE had an IL-2-specific increase in the levels of IFN-gamma and
GM-CSF. Taken together, these findings indicate that i. p. treatment of ovarian
tumors with
IL-2 pDNA:
DMRIE/DOPE can lead to an increase in local
IL-2 levels, a change in the
cytokine profile of the
tumor ascites, and a significant antitumor effect.