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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