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Liver an Excellent Target For Cancer Gene Therapy

A study demonstrates that cancer cells in the liver are excellent targets for gene therapy using adenoviral vectors//. It is based upon a fundamental new understanding of the differences between cancerous and normal liver cells. The findings signal a new way to treat cancers that have spread to the liver, such as metastatic cancers of the colon and breast.

The research team, led by Tony Reid, M.D., Ph.D., of the Moores Cancer Center at University of California, San Diego (UCSD), reports that in normal liver cells there is only one receptor – or doorway the vector uses to enter the cell. This doorway is located at the base of normal liver cells, hidden from the blood vessels. The research also demonstrates that in cancerous cells the receptor for adenovirus, called the coxsackie-adenoviral receptor or CAR, is expressed randomly over the surface of the cell and is exposed to the blood vessels.

“Since the receptor is distributed randomly on the surface of tumor cells, the doorway is open for the adenoviral vectors circulating in the blood stream to infect and kill these cells,” said Reid, who was at Stanford University when this work was conducted. “At the same time, normal liver cells are protected. These findings may signal a new way to treat any cancer that has spread to the liver.”

Reid explained: “We are taking advantage of a fundamental characteristic of cancer cells – structural disorganization. The disorganized structure of the cancer cells exposes the receptors so that Onyx-015, the adenoviral vectors used in this study, can readily enter tumor cells. This may be the first time a therapy has been directed against the disorganized nature of cancer cells.”

Reid and his colleagues undertook this study following the death of Jesse Gelsinger, a participant in a gene therapy clinical trial at University of Pennsylvania for ornithine transcarbanoylase (OTC) deficiency, a metabolic liver disorder. That case virtually sto
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