[Homestead] Measles virus to destroy cancers---Mayo Clinic
tvoivozhd
tvoivozd at infionline.net
Mon Feb 7 08:03:42 EST 2005
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/Source:/ *Mayo Clinic*
/Date:/ 2005-02-05
/URL:/ http://www.sciencedaily.com/releases/2005/02/050204121548.htm
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Mayo Clinic Researchers Create 'Obedient Virus'; First Step To Use
Measles Virus Against Cancer
ROCHESTER, Minn. -- An international team of Mayo Clinic-led researchers
is first to devise a system that consistently converts the measles virus
into a therapeutic killer that hunts down and destroys cancer cells --
and cancer cells only. Their research findings appear as an advanced
electronic article of Nature Biotechnology.
The researchers harnessed the viral trait for attacking and
commandeering cells, and then redirected the virus to attack diseased,
rather than healthy cells. The work was done on laboratory animals
implanted with two kinds of human cancer cells -- ovarian cancer and
lymphoma -- and is probably still years away from use as a human
therapy. But the concept has at last been proved in mice with human
cancer tumors -- and that's an essential step toward using this approach
to expand and improve human treatments for a variety of cancers.
*The "Obedient Virus"*
"When I saw the data, I was completely stunned. It's the sort of thing
that, having worked on targeting viruses for about 15 years, I just
couldn't believe that we'd finally got what we'd been hunting all that
time," says Stephen Russell, M.D., Ph.D., lead researcher and director
of Mayo Clinic's Molecular Medicine Program.
"It's very clean, very clear targeting. Our results show that we've
efficiently ablated (destroyed) the ability of the measles virus to
interact with its two natural receptors. And they also show that we can
take our pick as to what new receptor we target and send the virus after
it."
*How They Did It*
Using bioengineering techniques, the team reprogrammed the measles virus
to seek a cancer cell to bind to instead of its natural binding partner.
Then they invented a "molecular tag" that they attached to structures on
the outside of the cancer-seeking measles virus. This tag is the key
innovation of their work and central to the success of the team's
investigation. It enables researchers to grow retargeted measles virus
on special "universal substrate cells" -- while at the same time
conserving the viral component for targeting and destroying tumors. Mass
production of a retargeted virus was not possible before this specific
innovation of the molecular tag -- and research in this area was at an
impasse. Not any more.
"The virus goes where it's meant to go, and it destroys the tumors in a
targeted way," says Dr. Russell.
*Background Biology*
Natural viruses are cellular parasites. To reproduce more viruses, they
need to bind to a partner on their target cell, fuse membranes to enter
the target cell and then take over the cellular machinery. When they
succeed in doing this, an infection occurs. Viruses are so good at
taking over cells that researchers have long dreamed of exploiting the
specific attraction viruses have to certain cells and using it as a
homing device to seek and enter cancer cells.
The measles virus became the focus of this vision several years ago when
the surprising finding was made that the measles strain used
internationally for vaccinations has natural anticancer activity.
"But we had a concern that the measles virus may be a little too
promiscuous in its ability to infect both cancer cells and non-cancer
cells, so we wanted to develop a method whereby we could retarget the
virus to infect cancer cells only," says Dr. Russell. "And we succeeded."
*Collaboration and Support*
In addition to Dr. Russell, the Mayo Clinic research team includes
Takafumi Nakamura, Ph.D.; Kah-Whye Peng, Ph.D.; Mary Harvey, Suzanne
Greiner and Charles James. From the University of Ottawa, Ian A.J.
Lorimer, Ph.D, contributed his expertise. The work was funded by The
Mayo Clinic Foundation, the Harold W. Siebens Foundation, and the
National Cancer Institute.
# # #
To obtain the latest news releases from Mayo Clinic, go to
http://www.mayoclinic.org/news. MayoClinic.com
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