[tt] Cancer-Killing Virus Modified to Deliver a One-Two Punch

[Brian Atkins]

http://www.wired.com/medtech/genetics/news/2007/10/cancer_virus

Scientists hacking a smallpox-like virus into doing battle with cancer have 
given a new weapon to their microscopic warrior.

Researchers at Stanford University and Jennerex Biotherapeutics have tweaked the 
cancer-killing vaccinia virus JX-963 so that it also stimulates the body to 
generate cancer-fighting white blood cells. The company intends to take the 
virus into clinical trials based on a promising animal study.

"This is a very powerful and potent approach," said Dr. Antonio Chiocca, a 
professor at Ohio State University and a specialist in oncological neurosurgery, 
who was not involved in the study. "You can think of each of these viruses as a 
new drug."

Cancer-fighting viruses are the latest attempt to harness viruses' infectious 
powers for therapeutic treatments. Modified viruses have been used in 
experimental gene therapies to "fix" faulty inherited genetic code. Gene therapy 
has generated much hype but little clinical success. Scientists claim to have 
made recent progress targeting cancer cells with modded cold, herpes and 
smallpox viruses. These viruses infect and kill cancer cells while leaving 
healthy cells alone. A different Jennerex virus, JX-594, is already entering 
Phase II clinical trials for the treatment of liver tumors.

In a study appearing Thursday in the Journal of Clinical Investigation, the 
researchers report that the new JX-963 treatment resulted in the suppression of 
colon tumors in the rabbits on which it was tested.

"The results are very encouraging," said Dr. Stephen Thorne, a co-author of the 
study and professor of surgical oncology at the University of Pittsburgh. "I 
would envisage clinical trials starting next year."

Thorne is a Jennerex consultant.

Until now, virus therapies have had limited success targeting and killing all 
the cancer cells in the body, and not just some. With the new JX-963 therapy, 
the virus doesn't have to do the work alone -- it elicits the body's own 
defenses to mop up cancer cells.

The chemical that the virus secretes, granulocyte-macrophage colony-stimulating 
factor, or GM-CSF, is a protein that stimulates the production of white blood 
cells. The scientists must be careful, however, not to overstimulate the immune 
system so that it kills the virus before it has a chance to attack the cancer.

"You have to make sure you give the virus enough time to do its job," said Chiocca.

Paradoxically, the answer might lie in temporarily suppressing the immune system 
with drugs to allow the virus to spread rapidly. Then, after the virus has 
destroyed most of the tumor, GM-CSF stimulates an elevated immune system response.

The obvious risk of using viruses to attack cancer cells is that the virus might 
mutate into a deadly form. Since a death in a clinical trial in 1999, 
gene-therapy research has been on the back burner. Similar problems in the field 
of cancer-killing viruses could halt research.

Chiocca downplayed the risk from viruses that target humans, like the one used 
by the Stanford researchers. He said that most people already have been exposed 
to the smallpox, cold and herpes vaccines, so our immune systems are unlikely to 
be compromised by any of their forms.

However, there are more risks when researchers use viruses that attack other 
species. There are a small number of preclinical trials using viruses that don’t 
target humans, Chiocca said.

"You worry about injecting a bird virus into humans, which could potentially 
become adapted to the human population and create a supervirus," he said.

-- 
Brian Atkins
Singularity Institute for Artificial Intelligence
http://www.singinst.org/