Loss of coxsackievirus and adenovirus receptor (CAR) is frequently observed in malignant cancer, hampering adenoviral gene therapy approaches. Complexing adenovirus with cationic liposomes can increase adenoviral transgene expression, particularly in cells with CAR-deficiency. We investigated whether other factors such as lipid composition might be involved in determining the efficiency of liposome-complexed adenoviral gene transfer in cancer cells.
Material and methods
Human cancer cell lines with different expression levels of CAR were infected with a GFP transgene. The efficiency of transgene expression was assessed by determining GFP expression using FACS analysis.
The efficiency of liposome-complexed adenoviral gene transfer was dependent on the lipid composition constituting liposomes. Polyethylene glycol (PEG)-containing liposomes were most effective in increasing liposome-complexed adenoviral gene transfer. In CAR-deficient cells, use of PEG-containing liposomes enhanced adenoviral gene transfer, whereas in CAR-expressing cells enhancement varied depending on cell type. In some CAR-expressing cells, the effect of liposome complexing was even comparable to that in CAR-deficient cells. Increased adenoviral transgene expression following complexing with PEG-containing liposomes correlated with liposome uptake in cancer cells.
Liposome-complexed adenoviral gene transfer appears to depend on lipid composition and the level of liposome uptake by cancer cells, in addition to CAR levels. Our study suggest that these multiple factors should be considered in designing liposome-complexed adenoviral vectors to improve outcomes of current adenoviral cancer gene therapies.
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This work was supported by a research grant from the National Cancer Center
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Lee, E.M., Hong, S.H., Lee, Y.J. et al. Liposome-complexed adenoviral gene transfer in cancer cells expressing various levels of coxsackievirus and adenovirus receptor. J Cancer Res Clin Oncol 130, 169–177 (2004). https://doi.org/10.1007/s00432-003-0521-z
- Gene therapy
- Polyethylene glycol
- Coxsackievirus and adenovirus receptor