Hybrid virus - being tested in dog

http://www.chron.com/disp/story.mpl/front/3811517.html
April 22, 2006, 1:20AM
Hybrid virus may help fight cancer
Local scientists find that it shows promise as a way to target tumors

By ERIC BERGER
Copyright 2006 Houston Chronicle

Using the cell-invading prowess of viruses and the hybrid concepts driving
up automobile fuel efficiency these days, local scientists have found a
way to light up cancerous tumors in mice like fireflies in the night.

What sounds like a genetics parlor trick may be an important step toward
identifying cancer cells and zapping them before they spread and smother
healthy organs.

By creating a hybrid out of two dissimilar viruses, researchers hope to be
able to illuminate tumor cells, making it easier for doctors to target
cancers and monitor treatments.

It also could provide a kick-start to the unfulfilled promise of gene
therapy.

"This really bridges a big gap," said Renata Pasqualini, a professor of
medicine and cancer biology at The University of Texas M.D. Anderson
Cancer Center, co-leader of a study published in Friday's issue of the
journal Cell.

That gap ? the successful delivery of genes into cells ? has been the
primary reason medical researchers have failed to get gene therapy to live
up to its potential.

Genes, the carriers of hereditary information, signal a body's cells when
it's time to manufacture certain proteins. These proteins carry out the
basic biologic functions of life.

Scientists long have thought that inserting normal genes into cells to
replace the function of defective genes, such as restoring insulin
production in the case of diabetics, could treat diseases.

But they have struggled to capitalize on the trove of information on the
25,000 human genes accumulated in the past decade, largely because of the
delivery problem.

Viruses by nature attack human cells to introduce their genes into the
host cell for the purposes of replicating and spreading throughout the
body. Scientists already have tapped that ability.

But viruses have proved to be imperfect carriers of "good" genes because
they attack human cells indiscriminately, both the healthy and cancerous.
Moreover, the body's immune system often is good at destroying these
viruses before they reach their targets.

These shortcomings have led scientists to look a little further down the
food chain to viruses that infect bacteria. Such viruses are found
everywhere, from soil to the human gut.

Bacterial viruses can be targeted very specifically to different types of
cells. But because they've evolved to infect bacteria, these viruses do a
poor job delivering good genes into human cells.

What's a biologist to do? Combine the best features of both viruses into
one.

The hybrid virus created by Pasqualini and her colleagues at M.D. Anderson
infected nearly 100 percent of the targeted cancerous cells, and the genes
they delivered functioned for weeks or even months, a stunning success.
The delivered genes produced fluorescent proteins that the researchers
could easily see with imaging equipment.

With the new technique, Pasqualini said, it could be possible for cancer
doctors and their patients to know almost immediately whether chemotherapy
and other treatments are having any effect on tumors.

It's worth noting, however, that there have been past successes with small
animals that haven't translated into larger mammals or humans.

"This is only a proof-of-concept" cautioned Dr. Wadih Arap, a co-leader of
the study along with Pasqualini.

Still, the research has garnered the attention of other cancer scientists.
Not only does it appear to have solved the problems of targeting and
delivery, but the hybrid virus seems to evade the body's immune system
long enough to deliver its genetic payload.

"I have a lot of excitement for this new approach," said Dr. Steven
Libutti, a senior investigator at the National Cancer Institute and head
of its Tumor Angiogenesis Section.

Libutti and other researchers are testing the hybrid virus in dogs with
cancerous tumors. In the study, Libutti has begun using the hybrid virus
to transport genes that produce a protein-like material that's toxic to
cells that line blood vessels leading to tumors. Kill the blood vessels
and the tumor starves.

Performing the study in large animals is the final step before the hybrid
virus can be tested in humans, possibly within a few years.

"We've treated the first dog in this study without any toxicity," Libutti
said. "We should know s

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