Engineered virus could be ideal for targeting cancers with lethal gene therapy

Scientists from Cancer Research UK have taken advantage of the selfish behaviour of cancer cells to target them with a genetically engineered virus.

If infected, normal cells altruistically shut themselves down to contain the virus, but cancer cells refuse to stop for anything – allowing the virus to thrive. Researchers found it was able to spread throughout tumours, leaving healthy tissue untouched.

Reporting their results in the June issue of Molecular Therapy, the authors suggest that the engineered virus could be ideal for targeting cancers with lethal gene therapy, opening the way for new, highly selective anti-cancer treatments.

Viruses work by infiltrating and then killing cells. Their ability to enter cells undetected makes them an attractive prospect for carrying anticancer treatment directly into tumour cells. The trick is to protect healthy cells from the process.

The GM virus was created by removal of a gene (called E1B-19kD) that viruses use to disguise themselves, and which prevents cells from noticing they have been infected.

Removal of the gene exposes the virus. Normal cells recognise they are under attack and commit suicide, preventing the virus from spreading to their neighbours. But cancer cells are programmed to resist suicide and do not die when infected – selfish behaviour that enables the GM virus to replicate and spread through tumour tissue.

Scientists from the Cancer Research UK Clinical Centre at Barts and The London, Queen Mary's School of Medicine and Dentistry, tested the virus on cells grown in the laboratory and in model tumour systems. It thrived in cancerous tissue, reproducing and spreading infection, but was eliminated from healthy tissue.

The system appears to overcome one of the major stumbling blocks of viral cancer treatment, by achieving higher levels of infection in tumour tissue than other therapeutic viruses without putting healthy tissue at risk.

"The great thing about this strategy is that the cancer cell does all the hard work," explains team leader Professor Nick Lemoine, who is Director of the Cancer Research UK Clinical Centre.

"It makes more and more virus to infect its neighbouring cancer cells. If a normal cell is infected it commits suicide before it can make new virus, its neighbours don't get infected and spread of the virus is contained.

"The next step is to put a toxic gene into the virus, so we can poison tumours while leaving normal tissues unharmed."

An advantage of this design is that it removes a gene, leaving more room to insert other genes that will enhance the ability of the virus to kill the cancer cells it infects.

Since the new virus proliferates selectively in tumours, researchers believe that only a small number of copies of the virus would need to reach a tumour for the treatment to be effective.

It might therefore be possible to inject the modified virus into the bloodstream of patients – unlike other viral therapies under development, which require injection directly into the tumour.

Prof Lemoine adds: "The virus we are using can replicate in tumour tissue much faster than its predecessors and offers real hope for the future. We plan to test it in clinical trials early next year."

Professor Robert Souhami, Cancer Research UK's Director of Clinical and External Affairs, says: "Although a tumour is derived from a patient's own body, there are key differences between normal cells and cancerous ones which we can exploit in developing new treatments.

"In this case, researchers have targeted cells with a virus which can only replicate and spread infection in the specific environment of a tumour. In tests so far it has proven both potent and selective, although only clinical trials will tell us whether the approach can be an effective treatment in people."