(thought ya'll might 'preciate) American Society for Microbiology General Meeting, Florida lifelines: Virus crosses brain cancer
TOM CLARKE
Glioma (green) could be caught by the virus cross.
What do you get if you cross the common cold virus with the polio virus? A precision tool for excising a virtually untreatable form of brain cancer,
researchers told this week's American Society of Microbiology's annual meeting in Orlando, Florida.
The viral chimaera targets the most common, and fatal, form of brain cancer, malignant glioma. Glioma occurs in the glia cells, support cells that are
diffused throughout the brain, making it impossible to remove surgically. And it does not respond to chemo- or radiotherapy. About 20,000 people are
diagnosed with the cancer in the United States each year.
Finding that a protein — CD155 — that invites poliovirus into cells is also produced by malignant glioma cells, Matthias Gromeier and colleagues at
Duke University in Chapel Hill, North Carolina, set to work.
They created a hybrid poliovirus that targets and destroys malignant glioma in mice but does not cause polio in primates, an animal model for polio in
humans. "This could be a dream come true for people working on brain tumours," Gromeier says.
"It's quite beautiful work," says Alice Wong, a microbiologist at the California Institute of Technology in Pasadena. "It's an approach to curing disease
that shows great promise."
The US National Cancer Institute is now supporting the Duke team to prepare a prototype antitumour virus for future clinical trials in patients with
incurable malignant glioma.
Previously, Gromeier genetically modified mice to produce CD155 in specific nerve cells. Wild poliovirus stuck to, entered and exterminated these
cells. Gromeier recalls: "We realized we could exploit the natural ability of this remarkable pathogen to kill specific cell types."
CD155 is an excellent target for the killer. It is produced only during brain development and disappears in the mature brain. So it is present solely in
adult brains afflicted with glioma.
However, wild-type poliovirus infects motor neurons in the human central nervous system, causing paralysis and sometimes death. So, to exploit the
virus, Gromeier's team first had to tame it.
By splicing a region of a human rhinovirus, which causes colds but cannot infect nerve cells, into wild poliovirus, they produced a more disciplined viral
half-breed — one that does not cause polio but does destroy glioma cells.
Gromeier's team implanted CD155-producing malignant glioma tumours into mice and then injected the hybrid virus into the animals' spinal fluid. A
single dose of virus shrank the tumours dramatically within seven days. After eight days they couldn't be detected at all.
Mice do not naturally produce CD155, so the team assessed the safety of the virus by infecting 14 primates with it. Like humans, primates produce
CD155 during embryonic development. "None of them showed any signs of weakness or other symptoms associated with poliomyelitis," says
Gromeier.
But before clinical trials can start, Gromeier's team must put their hybrid virus through a few more hoops. They are now investigating the possibility that
their chimaera might recombine with wild-type poliovirus or live oral polio vaccine — though rare, both are present in the environment — and revert to
a pathogenic form. |
