Genetically engineered virus shrinks cancerous liver tumours in humans

US scientists have shown that therapies based on genetically engineered vaccinia virus, a complex virus belonging to poxvirus family, have the potential to treat liver cancer.

David Kirn at Jennerex Biotherapeutics in San Francisco, California, has revealed that a 'tail' composed of a protein called actin gives the genetically tailored virus the capability to spread more easily within cancer tumours than previously employed viruses.

In the first step of their research, the researchers deleted a gene from the vaccinia virus to render it unable to produce an enzyme called thymidine kinase, without which the virus could not replicate and cause damage to normal, healthy tissue.

However, cancerous cells contain thymidine kinase in abundance, and thus make it easy for the modified vaccinia virus to multiply within tumours. According to the researchers, once the virus creates enough copies of itself, it bursts the cancer cells where it resides.

The researchers then added a gene to the virus that made it produce a signalling molecule called cytokine, which attracts the body's immune cells towards tumours. As a result of the whole process of genetic engineering, they got a tumour-targeting vaccinia virus known as JX-594.

In July 2006, the researchers started treating 13 patients with advanced liver cancer by administering the JX-594 virus directly into their tumours every three weeks, reports New Scientist magazine.

Seven of the participants survived for more than eight months, of whom three are still alive over 15 months later, said the researchers.

The findings attain significance as all previous therapies showed an expected survival of only three to four months.

According to the researchers, the virus shrank the tumour in 10 of the 13 patients in the trial, with five subjects experiencing a greater than 50 per cent reduction in tumour size.

Kirn revealed that the only notable side effect experienced by the participants was temporary flu-like symptoms from the JX-594 injections.

His team has also used another modified vaccinia virus called JX-963, which is a nearly identical virus to JX-594, to reduce liver tumour growth in rabbits. More than 80 per cent of the animals treated with the JX-963 showed a greater than 50 per cent reduction in tumour size.

Encouraged by the positive results from the preliminary clinical trials and recent animal experiments, Kirn's team is now planning to conduct phase II trials to determine whether the JX-594 virus can help treat other types of tumours like cancers of head and neck.

The researchers presented their findings at the Molecular Targets and Cancer Therapeutics meeting, partly sponsored by the American Association for Cancer Research, in San Francisco, California. (ANI)

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