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HealthVaccines will curb cancers


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The Australian — HealthVaccines will curb cancers, not cure them

The first vaccine to prevent cancer will soon be in use. Does this mark a turning point in the treatment of the disease? Nigel Hawkes reports

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June 24, 2006

A DREAM that has inspired cancer researchers for more than a quarter of a century has come true. The first vaccine to prevent cancer has won a licence and will be in use by the end of the year.

The approval by the US Food and Drug Administration (FDA) of Gardasil, a vaccine to prevent cervical cancer, has re-awakened interest in the whole field of cancer vaccines. Gardasil, from pharmaceutical giant Merck, and its rival Cervarix, from GlaxoSmithKline (GSK), will prevent infection by the human papilloma virus, which causes cervical cancer.

They will save thousands of lives every year. Gardasil - based on discoveries by Australian of the Year Ian Frazer and developed by Melbourne-based company CSL which licensed international sales to Merck - could be available in Australia as early as August. True, cervical cancer is a special case, as it is known to be caused by a virus. Most cancers are not, so simple vaccines to prevent and treat them are less readily devised. But after years of disappointment, hopes are rising that vaccines against a wide range of cancers may prove effective. Is the tide turning? Some eminent people people think so.

Last week GSK announced results from a trial of its lung cancer vaccine, which, compared with a placebo, produced a one-third reduction in the chances of cancer recurring after surgery. Lung cancer is one of the toughest cancers to treat, so these results - though not statistically significant - were ``very encouraging'', GSK said. Bigger trials will follow.

Other straws in the wind include good results in tackling prostate and skin cancers, and non-Hodgkin's lymphoma. If the scale of effort is any guide, cancer researchers and drug companies believe that vaccines can at last make a real contribution. There are more than 100 cancer vaccines in late-stage development from more than 75 companies, and although many will fail, in the next five years about 50 should be launched, analysts believe.

Cancer specialists foresee the day when cancer will be ``just another disease,'' not the death sentence that it used to be. There will be cures, but most patients are unlikely to be cured completely. For them, it will be a disease that they live with rather than die from.

Already the number of people in this group is growing fast, partly as a result of earlier diagnosis, partly longer survival. But by 2025 this group will be many times larger as cancer vaccines make it possible to blunt the disease's cutting edge. Unlike Gardasil and Cervarix, most cancer vaccines are designed not to prevent cancer, but to treat it.

The reason cancer can spread is that the immune system is often poor at recognising cancer cells as `foreign' and attacking them. Essentially, tumour cells appear normal to it - and even when an attack is launched, cancer cells can develop ways of ``hiding'', perhaps by reducing the number of proteins on the cell surface that are normally the targets of antibodies.

The aim of cancer vaccines is to restore or strengthen the immune system's ability to attack cancer cells. The idea is far from new but for many years made little progress. ``Twenty years ago, people didn't realise how little they knew about the immunology of cancer,'' says Jose Lutzky, a researcher at Mount Sinai Medical Centre in Miami Beach. Typically, early results were encouraging but the vaccines failed as soon as large trials were attempted. ``The whole field was riddled with high expectations,'' says one US researcher.

``Then everybody failed.'' Despite this, the idea remains so attractive that research has continued and is growing. Several different methods are being used. The simplest idea is to combine fragments of a cancer cell with an adjuvant - a material known to provoke the immune system into action - in hope that this will create a much stronger immune response. Another approach is to take specialised white blood cells from the patient, mix them with the cancer cells, then inject them back. Similarly, the idea is that these dendritic cells - the most powerful immune-inducing cells in the body - will help the immune system to recognise and attack the cancer.

Last year the first concrete success for a vaccine using dendritic cells was published. Provenge, made by a Seattle-based company, used dendritic cells taken from prostate cancer patients and engineered them to produce a protein found in about 95 per cent of prostate cancer cells. The trial showed that 34 per cent of men given Provenge, compared with 11 per cent on a placebo, were alive three years after treatment began.

The more aggressive the disease, the more effective it was. The manufacturer, the US biotech group Dendreon, hopes to submit data for approval by the FDA later this year. A different approach is to try to identify proteins that are unique to cancer cells and use them as the basis for a vaccine. One such protein, discovered by researcher Peter Stern at the Paterson Institute for Cancer Research in Manchester in the UK, is 5T4, the normal role of which is to help a developing embryo latch on to the mother's womb. He found that cancer cells reactivate this protein as part of their technique for spreading around the body.

Two cancer vaccines have since been made using 5T4. In kidney cancer patients one trial showed that the vaccine doubled the survival time. And in colorectal cancer a second vaccine using 5T4, made by Oxford BioMedica, provoked a strong immune response and caused tumours to shrink. Yet another approach exploits a molecule called CTLA-4 that regulates the immune response.

By inhibiting CTLA-4 - taking off the immune system's brakes - scientists at the US National Cancer Institute managed to shrink tumours in patients with malignant melanoma, a form of skin cancer. They used an antibody to block CTLA-4, accompanied by a cancer vaccine designed to promote the immune response.

In two out of 14 patients the tumours disappeared entirely, in others they shrank, but some patients showed no benefit. Such results are enough to keep scientists encouraged, but they are still a long way from practical products. The hope is that growing understanding of cancer will underpin the efforts to create vaccines and produce much better results.

The optimists include Stern, who says he is confident that cancer vaccines will be on the market in a few years to be used alongside traditional cancer drugs. Louis Weiner, of the Fox Chase Cancer Centre in New York, agrees. ``We have a lot of tools now,'' he says, ``but we have to learn how to use them properly.''

So far it has not really been possible to compare the survival of people given vaccines with survival across the board, because new cancer treatments are always given to those for whom all other treatments have failed. Ethically it would not be justified to take a patient off a treatment, even a poor one, to try an unproved vaccine. A vaccine that cures the disease appears unlikely.

Much more possible is that, along with drugs, vaccines will prolong survival and help turn cancer into a chronic disease. People with cancer may live for years or even decades, as HIV-positive people already do.

The Times

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