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BPI: What role does the adenoviral vector play?
Peng: Upon intratumor injection, Gendicine binds to the coxsakie adenovirus receptor (CAR) on tumor cells. Subsequently, Gendicine enters tumor cells via receptor-mediated endocytosis and begins to over-express the encoded exogenous p53 gene. The overexpressed p53 protein triggers multiple tumor fighting functions.
First, it induces tumor cell cycle arrest or apoptosis by functioning as a sequencespecific transcriptional-regulator that upregulates the expression of some anticancer genes and downregulates the expression of some oncogenes.
Second, it can directly induce tumor cell apoptosis.
Third, it can function as a tumor-antigen by stimulating human immune cells (cytotoxic T cells) to selectively kill cancer cells that over-express the p53 gene. It can also activate natural killer cells to kill uninfected cancer cells via bystander effects.
Fourth, the expressed p53 protein can downregulate the expression of vascular endothelial growth factor (VEGF) genes and MDR genes, which are involved in tumor progress, metastasis, and chemo-drug resistance. The expression of p53 gene is not activated in normal cells because its DNA is undamaged, thus minimizing the side effects of Gendicine treatment.
expressed exogenous p53 protein can be
detected by immunohistochemistry
analysis in the intestines, lungs, bladders,
and kidneys. At three weeks postinjection,
the p53 gene and the expressed p53 protein
were still detectable in the abovementione
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