MAY 15, 2006
VOLUME 3 NO. 9

ADVANCES in MEDICINE

Vaccine stops deadly brain tumours
in their tracks

'Off-the-shelf' shot prolongs survival with
minimal toxicity


The prognosis for patients with glioblastoma multiforme (GBM) is grim at best. But a new vaccine that delays tumour progression and prolongs survival offers hope for those stricken with this deadliest of brain cancers. The research was presented at the annual meeting of the American Association of Neurological Surgeons on April 25.

Life expectancy for GBM patients undergoing the current standard of care — surgical resection followed by radiation and chemo — is a meagre 14 months. "The heterogeneity of the tumour makes it difficult to treat," explains study author Dr Amy Heimberger, a neurosurgeon at MD Anderson Cancer Center in Houston, TX. "Individual tumour cells are different, and it's also highly invasive, so it's hard to resect. It's like someone unscrewed a salt shaker and dropped it on the brain. You have little grains of tumour all over."

That's why she and many of her colleagues think a vaccine is the way to go. "The immune system has the ability to track those single cells and eradicate them or keep them at bay," says Dr Heimberger. Dr Richard Leblanc, director of McGill University's Brain Tumour Program, agrees. "With immunotherapy, you hope to avoid the complications of systemic treatment that are seen with chemo."

READY, AIM, FIRE
The study followed 23 patients, 21 of whom were vaccinated after having undergone surgery, chemo and radiation. The median time to tumour progression was 12.1 months in the vaccinated group, compared to 7.1 months for the unvaccinated cohort. Median survival was at least 19 months and only four patients died.

The vaccine targets EGFRvIII, a mutated version of the EGFR protein found only on the surface of the tumour cells. EGFRvIII enhances tumour proliferation and stimulates the growth of new blood vessels. But the vaccine recruits the brain's immune system to target EGFRvIII-bearing cells for destruction. "It's a very specific target, which reduces the risk of deleterious autoimmunity," says Dr Heimberger. She explains that tumour cells naturally exploit several mechanisms to suppress the immune response, so the vaccine helps give the body's natural defences that extra push. "That's why the first step in getting the vaccines to work is to surgically remove as much of the tumour as possible, to limit the presence of these suppressing factors."

The vaccine stands to make a big difference for the 30-50% of patients whose tumours express EGFRvIII. And so far, the results are promising: none of the recurrent tumours of vaccinated patients displayed the marker anymore. Dr Heimberger says this proves the vaccine worked. But she warns it could also foreshadow how the treatment may ultimately fail — if EGFRvIII is no longer present, the vaccine-stimulated immune cells won't find their mark.

Still, she isn't discouraged. "This isn't the only tumour-specific antigen," she says. "We'll soon be screening these tumours to see what antigen targets they'll be sensitive to, and we'll select the vaccine accordingly."

An important advantage of Dr Heimberger's vaccine is that it can be given 'off the shelf,' in three injections over a two-week period, followed by monthly boosters.

 

 

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