IL-2 plasmid therapy of murine ovarian carcinoma inhibits the growth of tumor ascites and alters its cytokine profile

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-hydroxyet hyl)-N,N-dimethyl-2,3-bis(tetradecyloxy)-1-propanaminium bromide/dioleoylph osphatidylethanolamine (DMRIE/DOPE), Reporter gene studies were initially c onducted in which mice bearing i.p. murine ovarian teratocarcinoma (MOT) we re injected i.p. with reporter gene plasmid DNA (pDNA):DMRIE/DOPE Histochem ical analyses revealed that transfection occurred primarily in the tumor ce lls of the ascites, with only a minority of other ascitic cells or surround ing tissues transfected, IL-2 levels in the MOT ascites were determined aft er i.p. injection of either IL-2 pDNA:DMRIE/DOPE or recombinant IL-2 protei n. 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 singl e 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 cytoki ne profile of the MOT tumor ascites revealed that mice treated with IL-2 pD NA: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 ovar ian 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 signif icant antitumor effect.