Technology : Trip the switch and kill the cancer

2019-02-27 05:07:05

By Andy Coghlan COLON cancers transplanted into mice have been persuaded to self-destruct by an experimental form of gene therapy. Pharmaceuticals giant Glaxo Wellcome devised the technique with the Cancer Research Campaign and hopes to begin trials in people within the next 18 months. First the mice are injected with a virus that smuggles a special gene into the animals’ cells. The gene makes an enzyme called nitroreductase. In the second stage, the mice are injected with a “prodrug”, codenamed CB1954. The compound is harmless until it meets nitroreductase, when it turns into a drug that kills the cancer cells. Martin Ford of Glaxo Wellcome and his colleagues engineered the nitroreductase gene to work only in cancer cells, so that the prodrug would only be activated in these malignant cells. They did this by tethering a molecular switch to the nitroreductase gene. This switch is overactive in tumour cells from the ovary and colon, but in healthy cells the switch is not tripped and the nitroreductase gene lies dormant. The researchers found that tumours can be eradicated even if the virus reaches only a small percentage of tumour cells. This is because of a phenomenon known as the bystander effect. Once activated, the drug spills out of the first cell and kills its neighbours. Tumours in mice shrank by 70 to 90 per cent when only between 5 and 20 per cent of the tumour cells made nitroreductase. “We found that a single, high dose of the prodrug killed cancers that expressed the enzyme,” says Ford. Karol Sikora, director of clinical research at the Imperial Cancer Research Fund,