Growth inhibition of an orthotopic glioblastoma in immunocompetent mice by cationic lipid-DNA complexes.
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.
Higgins
Robert J
RJ
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA. rjhiggins@ucdavis.edu
McKisic
Maureen
M
Dickinson
Peter J
PJ
Jimenez
Daniel F
DF
Dow
Steven W
SW
Tripp
Linda D
LD
LeCouteur
Richard A
RA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D002455:Cell Division / Q000276:immunology; D002784:Cholesterol / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007093:Imidazoles / Q000378:metabolism*; D007121:Immunocompetence; D007275:Injections, Intravenous; D050356:Lipid Metabolism; D008055:Lipids; D008081:Liposomes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010957:Plasmids / Q000235:genetics; D014185:Transplantation, Isogeneic; D014407:Tumor Cells, Cultured
C120715:1-(2-(9-octadecenoyloxy)ethyl)-2-(8-heptadecenyl)-3-(hydroxyethyl)imidazolinium; D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D007093:Imidazoles; D008055:Lipids; D008081:Liposomes; D004247:DNA; D002784:Cholesterol