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Cancer Research UK is funding research on adenoviruses to beat cancer

Cancer Research UK is funding research on adenoviruses to beat cancer

On the whole, adenoviruses don’t do us any favours.

These microscopic particles invade human cells, wriggle their way to the cell’s nucleus – and then hijack the cell’s internal machinery to replicate as rampantly as possible. They replicate so fast, in fact, they burst our cells open. They then spread around the body looking for new cells to invade.

This makes us feel pretty ill, and causes cold-like symptoms in most people (although some types can cause more severe symptoms).

However, it’s not all bad news.

On the plus side, adenoviruses are, by a quirk of fate, particularly good at infecting and destroying cancer cells. One reason for this is that our body’s immune system often ignores tumours, making them more susceptible to infection.

Viruses also have relatively simple structures that can be easily modified to make them behave differently. They can even be tweaked to form the basis of powerful new cancer treatments – something Cancer Research UK and others are investing in at the moment.

Adenoviruses could help beat cancer

The beauty of using viruses for treating cancer is that, in theory, even if a few particles reach the tumour, they can quickly replicate, magnifying their cancer-killing effect. This doesn’t happen with ‘traditional’ cancer drugs.

And after a few days, the immune system will get rid of the infective virus but hopefully take any infected cancer cells with it – another plus.

But there’s a snag. Adenoviruses can also infect healthy cells. So if they reach the liver, for example, they can infect and destroy liver cells, harming the organ and potentially causing long-term problems.

So a team of Cancer Research UK scientists led by Professor Leonard Seymour has modified an adenovirus called Ad5 so that it still infects and destroys cancer cells in mice, but can’t replicate in their liver cells. This means that the modified virus should be much safer to use, and makes a good candidate for further development.

Testing new treatments

Encouragingly, adenovirus research is moving out of the lab and into the clinic. There are a number of trials in the pipeline to test the use of adenoviruses as treatments for different cancers. This will be the first time these therapies have been tested in patients, and should begin late next year.

Ovarian cancer

The first trial is in the planning stages, and is not expected to start for a few years. It will test a treatment for patients with ovarian cancer that’s based on a modified adenovirus called VTP1 . The trial will be led by Cancer Research UK clinician, Dr Iain McNeish.

The idea is that the adenovirus will deliver a gene which will tell ovarian cancer cells to ‘commit suicide’ and die – while not harming healthy cells.

Beating the spread of bowel cancer

Depending on the results, VTP1 adenovirus therapy may be used in a second trial. This time, the virus will be tested for its potential to treat bowel cancer that has spread to the liver.

Head and neck cancer

A diagram to explain gene-directed enzyme/prodrug therapy (GDEPT; click to enlarge)

A diagram to explain gene-directed enzyme prodrug therapy (GDEPT; click to enlarge)

Professor Caroline Springer’s team – based at the Institute of Cancer Research and funded by Cancer Research UK – are planning another exciting trial. They’ve modified an adenovirus for use as part of a two-stage treatment for head and neck cancer.

First of all, a virus called Ad.CPG2 carries a gene for an enzyme called CPG2 (exogenous enzyme carboxypeptidase G2) straight to the tumour. This causes the enzyme to be produced within the tumour in large amounts.

Next a ‘prodrug’ – an ineffective form of a drug molecule – is injected into the tumour.

Now for the clever bit. The enzyme converts the prodrug into a fully-fledged chemotherapy drug, but only inside the tumour. This means the drug can act directly at the site of the tumour to destroy it but minimises the amount of ‘active’ drug that spreads around the body and harms normal cells. So in theory, there should be minimal side effects.

In very early laboratory research, the team has shown that this approach, known as GDEPT (‘gene-directed enzyme-prodrug therapy’) can shrink breast and bowel tumours.

There is also potential to tailor this technique for different cancer types using different prodrug-enzyme combinations.

Promising early results

Developing adenoviruses for use in cancer therapy is not simple or cheap. And there are obvious safety hurdles to overcome. But while it’s still early days, results so far are promising.

With trials on the horizon, in the not-too-distant future adenoviruses may prove to be a valuable tool in our bid to beat cancer.

Tthe trials mentioned here are still in the early stages of planning, and that can be a lengthy process.

However, there’s a database of current clinical trials on our CancerHelp UK website, where you can search for other trials that are going on. Remember you will need to discuss your eligibility for any clinical trials with your doctor.

Emma

Emma Rigby is a science press officer at Cancer Research UK


References:

Cawood, R., Chen, H., Carroll, F., Bazan-Peregrino, M., van Rooijen, N., & Seymour, L. (2009). Use of Tissue-Specific MicroRNA to Control Pathology of Wild-Type Adenovirus without Attenuation of Its Ability to Kill Cancer Cells PLoS Pathogens, 5 (5) DOI: 10.1371/journal.ppat.1000440


Hedley, D., Ogilvie, L., & Springer, C. (2007). Carboxypeptidase G2-based gene-directed enzyme–prodrug therapy: a new weapon in the GDEPT armoury Nature Reviews Cancer, 7 (11), 870-879 DOI: 10.1038/nrc2247
The first trial is in the planning stages, and is currently expected to start

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