Gene therapy using adenoviral vector containing the
endostatin gene is a promising strategy for advanced
cancers. However, host immune response to adenovirus and the lack of the requisite
coxsackie-adenovirus receptor (CAR) in many primary cells limit the in vivo application.
Liposome-complexed adenoviral vectors have proven to be useful for enhancing gene delivery in target cells that lack adenoviral receptors and avoiding a
neutralizing antibody response. Here, we investigated antitumor effects of
intravenous administration with
PEG-PE cationic
liposome-encapsulated recombinant human
endostatin adenovirus (Ad-hEndo) on CAR-negative
ovarian cancer. Electron micrography (EM) showed that these
liposomes efficiently encapsulated the vectors, allowing CAR-independent adenovector transduction. The results showed that the complex enhanced transfection efficiency of recombinant adenovirus. Prolonged systemic administration was performed in immunocompetent mice and did not induce significant antibody response. The antitumor effect with
PEG-PE cationic
liposome encapsulated with Ad-hE (Ad-hE/lipo) was evaluated in the human
ovarian cancer model. Systemic administration was well tolerated and resulted in marked suppression of
tumor growth in an established
ovarian cancer model, which was associated with a decreased number of micro-vessels and increased apoptosis of
tumor cells. Our study shows that
PEG-PE cationic
liposome-encapsulated Ad-hE (Ad-hE/Lipo) can be administrated intravenously and lastingly to inhibit angiogenesis, thus showing promising clinical application.