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Smart virus hunts down tumours wherever they are

A VIRUS engineered to target tumours might give doctors a weapon for hunting down cancers that have spread throughout the body.

Many groups worldwide are working on ways of using viruses to destroy tumours. GenVec, a biotech company based in Maryland, recently completed an initial clinical trial of an anti-cancer gene therapy that uses an adenovirus – a type of cold virus – modified to carry a gene coding for tumour necrosis factor (TNF), which triggers cell death.

Because this virus attacks healthy and cancerous cells indiscriminately, it is too toxic to inject into the bloodstream and must be injected directly into tumours instead. Even so, the virus blocked tumour growth in all nine of the patients in whom it was tried, while six out of nine untreated tumours in the same patients continued to grow, GenVec researcher Thomas Wickham told a recent gene therapy conference in Banff, Canada.

To get around the toxicity problem, Wickham’s team has now modified two proteins normally found on the virus’s shell so they bind to receptors common on tumour cells. Mice given injections of targeted virus lost much less weight than usual, a sign of lower TNF toxicity.

What’s more, the viruses were equally likely to end up in a tumour as in the liver. This is a massive improvement compared with the untargeted viruses, which mostly end up in the liver. This should greatly reduce any toxic side effects.

The real test will be whether the approach works in people. It looks promising: the amount of virus reaching the tumour via the bloodstream was roughly equal to direct injection of the untargeted virus. “I think we’ve crossed a clear hurdle, which is getting proof of principle. You can give something systemically, have it circulate and get possibly therapeutic levels to the tumour,” says Wickham.

The team also found that the viruses targeted the tumour better when injected into the lining of the abdominal cavity. Wickham suspects this is simply because the viruses are released more slowly into the blood. If so, this effect could be mimicked by a slow intravenous drip.

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