Suicide Gene Therapy Kills Bowel Cancer Cells

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Suicide Gene Therapy Kills Bowel Cancer Cells

25 May 2007

An innovative type of gene therapy has for the first time succeeded

in making bowel cancer cells commit suicide, according to a report in

Cancer Research* this week.

The therapy, developed by Cancer Research UK-funded scientists at The

Institute of Cancer Research, combines cutting-edge techniques to

target tumour cells. Known as GDEPT (Gene-Directed Enzyme Prodrug

Therapy), the treatment uses a virus to attack cancer cells.

But the researchers have added an extra gene to the virus. The virus

is programmed to switch on the gene only if it reaches a tumour. When

the gene is switched on, the virus produces a protein that activates

an otherwise harmless 'prodrug', given separately.

Because this drug is only activated in tumours, it selectively kills

only cancer cells. In normal tissue, the drug remains inactive, so

healthy cells are not affected.

This is the first time such a therapy has proved successful at

killing bowel cancer cells, albeit only in the laboratory. Cancer

Research UK and The Institute of Cancer Research are supporting the

development of the therapy, and hope to take it into early clinical

trials in the future.

Lead researcher, Professor Caroline Springer of The Institute's

Cancer Research UK Centre for Cancer Therapeutics, said: " We have

developed a smart method to selectively target cancer cells. Normal

cells are spared because the virus doesn't produce the protein that

activates the drug unless it is inside a tumour.

" The beauty of our approach is that the cancer cells are made to

commit suicide both by the virus and the activated drug †" the two

work in tandem. And once activated, the drug has the added bonus of

causing the virus to produce more of the activating protein, which

activates more of the drug, and so on. It's the first time we've seen

a 'positive feedback loop' like this in a GDEPT therapy. "

The drug damages DNA inside the cancer cells to the point where the

cells stop functioning. They have no choice but to shut down and die.

Another benefit of the therapy is that it doesn't just kill only the

cancer cells infected by the virus.

" We also see a significant 'bystander effect', " added Prof

Springer. " This means the cells killed by the virus or the drug

release signals into the tumour that tell neighbouring cancer cells

to die too. "

In lab experiments, mice with bowel tumours that received the therapy

lived twice as long as those that did not. The researchers suggest

their technique could one day be used as a treatment for advanced

bowel cancer that doesn't respond to standard chemotherapy.

Professor Toy, medical director of Cancer Research UK,

said: " GDEPT therapy has been in development for several years. But

this study shows the technique - always a smart therapy - is becoming

ever more sophisticated. For the first time it has been shown to be

effective at killing bowel cancer cells in a laboratory model of

human colon cancer. This is another stride towards the possible use

of GDEPT for cancer patients. "

* Cancer Research, Vol 67 Issue 10

GDEPT: an oncolytic adenovirus is injected into the bloodstream. The

virus's DNA contains an added gene for CPG2 (Carboxypeptidase G2) but

the gene is controlled so that it is only translated in the presence

of telomerase, an enzyme found in many cancers but much less so in

normal tissue. When the virus reaches a tumour that is producing

telomerase, the gene is translated and the virus produces the protein

CPG2.

Meanwhile a " prodrug " is injected. A prodrug is an inactive form of a

drug. In this case the prodrug, called ZD2767P, is activated by CPG2 -

hence it is only activated in regions of the body where the virus is

producing CPG2, i.e. in tumours.

The Institute of Cancer Research

The Institute of Cancer Research is Europe's leading cancer research

centre with expert scientists working on cutting edge research. It

was founded in 1909 to carry out research into the causes of cancer

and to develop new strategies for its prevention, diagnosis,

treatment and care. The Institute works in a unique partnership with

The Royal Marsden NHS Foundation Trust, forming the largest

comprehensive cancer centre in Europe. This relationship enables

close daily contact with those on the frontline in the fight against

cancer - the clinicians, the carers and most importantly, the

patients.

About Cancer Research UK

Together with its partners and supporters, Cancer Research UK's

vision is to beat cancer.

Cancer Research UK carries out world-class research to improve

understanding of the disease and find out how to prevent, diagnose

and treat different kinds of cancer.

Cancer Research UK ensures that its findings are used to improve the

lives of all cancer patients.

Cancer Research UK helps people to understand cancer, the progress

that is being made and the choices each person can make.

Cancer Research UK works in partnership with others to achieve the

greatest impact in the global fight against cancer.

www.cancerresearchuk.org

URL: http://www.medicalnewstoday.com