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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