MARCH 30, 2007
VOLUME 4 NO. 6

ADVANCES in MEDICINE

Sleeping virus attacks tumours from within

Epstein-Barr 'awoken' to wage war on cancer cells


Viral warfare on cancer has been a dream of researchers for many years. The theory is that if a virus — rigged with so-called "reporter genes" — could be introduced inside the tumour cells it would destroy them from within.

Now a team at Johns Hopkins has found a way to use Epstein-Barr viruses (EBV) already asleep inside tumour cells to selectively target treatment. A variety of cancers, including four types of lymphoma, nasopharyngeal and gastric cancers are more common in individuals who have latent EBV infections.

"The beauty of this is that you don't have to introduce any reporter genes into the tumour because they are already there," said radiologist and study author Dr Martin G Pomper in a statement issued by the American Association for Cancer Research.

The team found that either of two commercially available products — including the multiple myeloma drug bortezomib — could be used to 'awaken' the dormant virus and push it into the lytic, or reproductive, phase of its life cycle. Once that happens, the tumour cell will start to express viral thymidine kinase (TK), an important enzyme for EBV reproduction. But the protein can also be used to visualize the EBV-containing tumour cells — the radiolabelled chemical fialuridine (FIAU) will attach to TK, causing the cells to light up on a gamma camera.

The team tested the theory in mice with Burkitt's lymphoma, the cancer most often associated with EBV. "[Bortezomib] woke up the virus in the tumours, which increased viral load by 12-fold, all the while cranking out TK," Dr Pomper explained. "An injection of FIAU made it easy to image the tumours with virus in them."

The idea, of course, is not just to visualize the tumour cells but to destroy them. While in this instance, radio-labelled FIAU was used to image the tumour cells, the compound can be engineered to contain "therapeutic radionuclides" which would selectively destroy cells in which TK is expressed.

The technique is described in the March 1 issue of Clinical Cancer Research.

 

 

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