The world's first gene therapy trial to treat patients with pancreatic cancer is being launched in the UK. The therapy uses a "Trojan horse" technique to hit cancer cells with large doses of toxic drugs.

MetXia, developed by UK company Oxford BioMedica, consists of a retrovirus which has been modified to carry a gene for an enzyme that normally occurs in the liver.

Retroviruses only replicate in dividing cells, so the treatment mainly targets cancer cells. Once in the cell, the virus inserts the gene for the enzyme and the cell starts producing it. The enzyme then converts an inactive drug into a toxic form.

This obliterates the tumour cells, without harming normal ones. It also means a hugely increased dose of chemotherapy can be delivered to tumours, without patients suffering greater harmful effects.

"In the industrialised world there are at least a quarter of a million people a year dying from pancreatic cancer," says John Neoptolemos, professor of surgery at the University of Liverpool, UK, who is leading the trial. "The horrible thing about pancreatic cancer is that if you have advanced disease, and you usually do, you can predict the date of death within a matter of a few weeks."

Alan Kingsman, chief executive of Oxford BioMedica, says: "We are really excited about the pancreatic cancer trial. We have reason to believe that MetXia may be quite potent in that type of cancer."

Source of destruction

Work in animal models of pancreatic cancer and in the test tube have shown promising results for MetXia. And early clinical trials to test its safety in patients with breast cancer and melanoma have also been encouraging.

The modified retrovirus carries a gene for an enzyme known as cytochrome P450 which is essentially a detoxifying gene, says Neoptolemos. The enzyme converts an inactive chemotherapy drug called cyclophosphamide into toxic phosphoramide mustard and acrolein.

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