Wednesday, April 4, 2012

Virus-Based cDNA Can Cure Established Tumors

In laboratory tests on mice, a gene therapy vaccine successfully wiped out 80% of advanced prostate cancer without causing serious side effects.

The British researchers behind its creation said it was a 'completely new approach' and predicted that it could start trials on people within a few years. Unlike a conventional vaccine which is given to prevent infection with a virus or bacteria, the new treatment is used after someone has contracted cancer.

Vaccines work by stimulating the body’s immune system to recognize antigens - distinctive proteins that are found on surfaces of cells. Most vaccines are designed to teach the body to seek out and destroy viruses or bacteria. However, scientists are also investigating vaccines that provoke an immune response to cancer cells.

Researchers first created a library of thousands of randomly-selected snippets of genetic code (cDNA) taken from a healthy prostate and then inserted them into a virus. The modified virus was then cultured in a laboratory and then injected into the bloodstream of a mouse with prostate cancer.

When the mouse’s immune system was exposed to the modified virus, it produced an array of antibodies – each one geared up to recognize a different antigen on the surface of a prostate cancer cell, the researchers report in Nature Medicine.

Professor Richard Vile, of the Mayo Clinic in Rochester, Minnesota who took part in the study said: 'Nobody really knows how many antigens the immune system can really see on tumor cells.

‘By expressing all of these proteins in highly immunogenic viruses, we increased their visibility to the immune system. The immune system now thinks it is being invaded by the viruses, which are expressing cancer-related antigens that should be eliminated.’

Progress has already been made towards developing a similar vaccine treatment for melanoma, the most dangerous form of skin cancer.

Past attempts at gene therapy cancer vaccines often used just one gene from a tumor cell to stimulate the immune system. But finding the right gene has proved difficult. And using two or more genes has raised fears that the immune response would be too strong for the patient to handle.

The researchers used two versions of the vaccine – one based on human prostate tissue, the other using mouse tissue. Both worked, although the human version was more effective. Injecting the vaccine into the blood, rather than the tumor itself, appeared to prevent the immune system going into 'overdrive' and attacking healthy tissue.

Professor Peter Johnson, of the charity Cancer Research UK, which funded the Leeds team, said: 'Although the vaccine didn’t trigger the immune system to overreact and cause serious side effects in mice, it will need to be further developed and tested in humans before we can tell whether this technique could one day be used to treat cancer patients.'

Each year around 35,000 men in the UK are diagnosed with prostate cancer and 10,000 die from the disease.

Read more in Nature Medicine.

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