The effect of a cationic
liposome non-coding plasmid
DNA complex on the growth of an intracerebral
glioblastoma in an immunocompetent syngeneic mouse strain was evaluated. Previous studies of extraneural
tumors in mice have demonstrated that such complexes containing plasmid
DNA are capable of stimulating a potent Th-1
cytokine immune-mediated response with a dramatic inhibition of
tumor growth. A
DOTIM-
cholesterol cationic
liposome complexed to non-coding plasmid
DNA (EV-CLDC) was administered intravenously (i.v.) at weekly intervals to 6-week-old male mice of the B6D2F1 strain at either 3, 10 or 17 days post-inoculation (DPI) of 4C8
glioblastoma cells.
Tumor growth was monitored by volumetric image analysis obtained from sequential weekly magnetic resonance imaging studies of the brain. Experiments were terminated between 30 to 38 DPI. Terminal
tumor volumes calculated from histological sections directly correlated with
tumor volumes from corresponding MR images. The EV-CLDC administered at 3 DPI resulted in a statistically significant (P<0.0001) sustained inhibition of
tumor growth compared with
tumors in mice administered only individual components of the EV-CLDC. The EV-CLDC similarly inhibited growth of longer established
glioblastomas. Histopathologic evaluation of terminal
tumors did not find any
hemorrhage,
edema or
necrosis in either the EV-CLDC-treated or control
tumors. The results indicate that an i.v.-administered EV-CLDC can significantly inhibit the growth of a
brain tumor in immunocompetent syngeneic mice.