When bad guys turn good

Engineered adenoviruses prove effective at killing tumour cells

By Owen Dyer

In the 60s Hollywood classic Fantastic Voyage, when a diplomat who holds the secret to miniaturizing soldiers is wounded, a team of scientists are reduced to molecular size and injected into his brain to remove a lethal blood clot. We're not quite there yet, but scientists from St Louis University have created miniature soldiers that can be injected into the body to fight disease. Only these soldiers come in viral form.

More precisely, scientists have engineered a novel oncolytic adenovirus vector named VRX-009 that's designed to kill colon tumour cells. They've also created VRX-007, which can kill lung adenocarcinoma cells as well. They reported the results in the May 15 issue of Cancer Research.

"These engineered viruses kill cancer cells through a mechanism that's completely different from chemotherapy or radiation," said Dr William Wold, who headed the study. "These viruses have the potential to treat many cancers that are resistant to currently available therapeutics. It also may be possible to use these viruses in combination with other therapies to create novel treatment regimens."

The VRX-009 adenovirus replicates far more efficiently in colon cancer cell lines than in other kinds of cell lines. It's designed to kill cells that carry a mutation common in many colon cancers and it can efficiently kill cultured colon cancer cells, but not lung cancer cells. VRX-007, on the other hand, made short work of both types of cancer cells. Moreover, in an animal model of colon cancer, injections of either VRX-007 or VRX-009 into tumours stopped cancer growth in its tracks better than a negative control, achieving a fivefold and tenfold suppression of growth, respectively. VRX-007 also halted tumour growth in a lung cancer model of disease.

Louis Zumstein, PhD, director of research at collaborating company Introgen, said: "These preclinical data are very promising and support our belief that oncolytic adenoviruses have enormous potential as a new class of cancer therapies that may provide potent and selective killing of cancer cells. These data also illustrate the flexibility of engineered oncolytic adenoviruses to target selected tumour types with great specificity."

These viral vectors are probably a long way from entering the market. Safety and efficacy studies will have to be especially rigorous, particularly when it comes to introducing an adenovirus into the lungs. Nonetheless, a new avenue of cancer treatment may have just opened up.