Saturday, May 20, 2006

Cancer Destroyed by Antibody 'Triple Whammy'

Love those scientific medical terms like "triple whammy". :-) From

A new cancer therapy using a "triple whammy" of antibodies has shown unprecedented success in mice. Not only does the treatment destroy tumours – even when they have spread around the body – it also prevents the tumours coming back. And the approach should work for a range of cancers.

Success in mice is far from a guarantee of success in people, but human trials have now begun on one component of the therapy.

The research, by scientists in Australia and Japan, is “an exciting advance”, according to cancer biologist Carl June of the University of Pennsylvania, US: “This novel form of therapeutic vaccination would not only enable potent tumour eradication but also protect from recurrence.”

The idea of using the body’s immune system to kill cancerous cells is already routinely deployed. Our immune system contains killer white blood cells called cytotoxic T lymphocytes (CTLs), which single out and destroy tumours. But the body’s natural response to cancerous cells is often not strong enough to wipe out the tumour.

The new therapy, called TrimAb (triple monoclonal antibody) therapy, may solve that problem. Mark Smyth, at the Peter MacCallum Cancer Centre in Australia, Kazuyoshi Takeda, at the Juntendo University School of Medicine in Japan, and colleagues used a cocktail of three different antibodies.

The first attacks the tumour directly, by stimulating the receptor for a death-inducing protein on tumour cells, called TRAIL. The boost that strengthens the response comes from the other two antibodies which activate killer T-cells that pitch in to kill the tumour.

TrimAb cleared large breast tumours in 80% of the mice that received the treatment, while the tumour disappeared in less than 30% of mice that got either single antibodies or double antibody combinations. And furthermore, the therapy induced a complete cure in 60% of the mice in which the breast cancer had spread to the lungs, liver, and brain.

TrimAb causes T-cells to produce an immune molecule named interferon gamma. “This molecule is key to tumour destruction”, Smyth told New Scientist. While TrimAb elicited the killer molecule in the lymph nodes of treated mice, treatments with a single or a pair of antibodies did not. “TrimAb also recruits a higher frequency of CTLs to attack the tumour,” he adds.

Many cancers express TRAIL, so TrimAb is not just specific for breast cancers. In particular, says Smyth, it works for renal cancer and sarcomas, and colon cancer is a promising target.

TrimAb prevents the recurrence of cancer because destroying the tumours presents the immune system with antigens, priming it for the future. A specific advantage of this is that the immune system is then primed against that particular tumour.

Three antibody combinations have never been used in patients to treat cancers, says Smyth. Although the combination was non-toxic to mice, careful pilot testing of each component and combination needs to be done in human trials, he cautions. The team is now awaiting results of Phase I trials involving humanised anti-TRAIL antibodies.

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