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Altered Cold Virus Kills Brain Tumors


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Altered cold virus kills brain tumors in mice

WASHINGTON (AP) ? Scientists have genetically altered a common cold virus so that it can destroy the most lethal type of brain tumor while not harming healthy tissue nearby.

The experiment worked so well in mice that researchers hope to begin studying it in people with this aggressive brain tumor, called a glioblastoma, late next year.

 

The scientists implanted human glioblastomas inside the brains of mice, then injected the experimental virus directly into the tumors. Untreated mice died in 19 days, but 60% of the treated mice were alive and thriving for four months.

 

Then scientists euthanized the survivors to see what was happening inside their brains ? and found only empty cavities and scar tissue where the tumors once were.

 

"Everyone here is excited about it because we've never seen anything happen with the mice like that," says lead researcher Dr. Frederick Lang, a neurosurgeon at Houston's M.D. Anderson Cancer Center.

 

He cautioned that the dramatic results don't assure the virus will work in people: Scientists have cured lots of mice of cancer only to see the therapies fail in patients.

 

"This is an interesting study," said Dr. Len Lichtenfeld of the American Cancer Society. But he echoed Lang's caution, adding that mutant viruses could prove too toxic to use.

 

"We need to be very, very careful" in studying the experimental treatment, Lichtenfeld said. "There are too many situations where doctors and patients and families have gotten very, very excited about drugs and it's turned out ... that the drugs weren't effective. We need to avoid that."

 

Still, the National Cancer Institute is intrigued enough that it is providing $1 million to produce enough of the mutant virus to begin human testing, said Lang, who hopes to start enrolling brain-tumor patients in a study of the treatment by winter 2004.

 

The virus should target other solid tumors, too, he said.

 

But "if there's any disease that needs a novel approach, it's really brain tumors," said Lang, who reported the experiment in this week's Journal of the National Cancer Institute.

 

Glioblastomas are the most common primary brain tumor in adults, striking about 7,000 Americans a year, and the most lethal. Survival is only about a year, a dismal rate that hasn't changed in decades despite improvements in surgery and radiation and chemotherapy treatments.

 

So how could the mild, sniffle-causing adenovirus tackle such a killer?

 

Before the immune system detects and eliminates a cold, adenovirus spreads by infecting a cell and hijacking its reproductive machinery to make viral copies, killing the cell in the process.

 

The key is to harness the adenovirus so it infects only tumor cells and not healthy tissue, something scientists have tried with limited success since the mid-1990s.

 

This latest attempt uses a different approach.

 

In normal cells, the retinoblastoma, or Rb, protein helps block an invading virus from reproducing. Rb protein also can block the uncontrolled cell division that is cancer's hallmark ? and thus solid tumors lack properly functioning Rb.

 

Adenovirus contains a gene that disables Rb so it can take over healthy cells. M.D. Anderson's Dr. Juan Fueyo altered that gene, leaving a virus capable of infecting Rb-lacking cancer cells but not healthy cells.

 

However, that mutant virus was relatively weak. So the next step was another genetic alteration that made it easier for the adenovirus to invade by binding to molecules called integrins that are common on the surface of cancer cells.

 

The resulting virus, dubbed "Delta-24-RGD," swept through some ? but not all ? of the mouse brain tumors like a wave, leaving dead cancer cells in its wake.

 

The big question is whether people's immune systems will attack the mutant virus before it can penetrate and spread through a brain tumor. The virus would have to be injected through the skull directly into the brain tumor, which could delay the immune reaction.

 

"It's going to be a race," Lang said. But "our studies suggest that there's a certain window of time between the immune system gearing up and the virus being stopped."

 

You can read about Dr. Lang Here

 

Another version...

"WASHINGTON (AP) - Scientists have genetically altered a common cold virus so that it can destroy the most lethal type of brain tumor while not harming healthy tissue nearby. The experiment worked so well in mice that researchers hope to begin studying it in people with this aggressive brain tumor, called a glioblastoma, late next year. The scientists implanted human glioblastomas inside the brains of mice, then injected the experimental virus directly into the tumors. Untreated mice died in 19 days, but 60 percent of the treated mice were alive and thriving for four months. Then scientists euthanized the survivors to see what was happening inside their brains - and found only empty cavities and scar tissue where the tumors once were. "Everyone here is excited about it because we've never seen anything happen with the mice like that," says lead researcher Dr. Frederick Lang, a neurosurgeon at Houston's M.D. Anderson Cancer Center. He cautioned that the dramatic results don't assure the virus will work in people: Scientists have cured lots of mice of cancer only to see the therapies fail in patients. "This is an interesting study," said Dr. Len Lichtenfeld of the American Cancer Society. But he echoed Lang's caution, adding that mutant viruses could prove too toxic to use. "We need to be very, very careful" in studying the experimental treatment, Lichtenfeld said. "There are too many situations where doctors and patients and families have gotten very, very excited about drugs and it's turned out ... that the drugs weren't effective. We need to avoid that."

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So, Dr. Lang... I know us Pit Patients don't have malignant brain tumors... but what about a virus for pit tumors?"

 

(nose against the glass)

 

 

"Smart Virus Eliminates Cancer in Animal Experiments

 

A research team led by M. D. Anderson has tested a novel ?viral smart bomb? therapy that can completely eradicate brain tumors in mice while leaving normal brain tissue alone.

 

The therapy, known as Delta-24-RGD, is thought to be the first treatment for malignant glioma, the deadliest form of brain cancer. It is a new-generation ?replication-competent oncolytic? adenovirus therapy, defined as a therapeutic virus that can spread wavelike throughout a tumor, infecting and killing cancer cells. There is no adequate treatment for these deadly brain cancers. Before this study, few experimental therapies tested in animals have shown much improvement.

 

The findings, published in the May 7 issue of the Journal of the National Cancer Institute, are considered so promising that the National Cancer Institute is providing financial support to produce, in its own labs, a drug-grade version of the therapy to test in humans, possibly by late next year. Researchers also are collaborating with the U.S. Food and Drug Administration on the treatment.

 

?We believe this therapy has a lot of potential, but one that needs much more study,? says lead author Juan Fueyo, M.D., an assistant professor in the Department of Neuro-Oncology and the study?s lead author. ?We've never seen this kind of response before with any other treatment tested in either animals or humans.?

 

Delta-24-RGD is designed in such a way that it can replicate only in cancer cells, not healthy tissue, in order to reproduce itself while killing the host cancer cell. It moves on to contaminate other tumor cells, and when no more cancer cells are left to infect, the virus itself dies.

 

?Biologic viral therapy like this may be just what we need to treat a complex disease like cancer,? says Frederick Lang, M.D., an associate professor in the Department of Neurosurgery, a primary investigator of the study. ?Cancer can be devious in that it does everything possible to evade destruction. But viruses are equally tricky in their quest to invade cells and propagate.

 

?In this experimental war between cancer and a viral therapy, the virus won,? Lang says. ?Of course, we hope to obtain similar results when patients are tested, but we cannot predict such success based on animal studies.?

 

Fueyo, Lang and a team of researchers from M. D. Anderson, the University of Alabama at Birmingham and the Institut Catal? d?Oncologia in Barcelona, Spain, found in repeated experiments that more than half the mice that had human glioblastoma tumors implanted in their brains and treated with Delta-24-RGD survived more than four months, whereas untreated mice lived less than three weeks.

 

The mice were considered clinically cured of their brain tumors. Investigators found only empty cavities and scar tissue where the tumors had been.

 

Recent advances in the understanding of brain tumor biology have led researchers to target molecular defects in brain tumors. At M. D. Anderson, researchers have focused on a gene and protein product that malfunctions in nearly all malignant gliomas as well as in many other solid tumors: the retinoblastoma (Rb) protein. Found in all cells of the body, an Rb protein acts like a brake on cell division by preventing certain other regulatory proteins from triggering DNA replication. If the Rb protein is missing or nonfunctioning, a cell can replicate itself over and over, resulting in the development of a tumor.

 

In normal cells, the Rb protein also prevents a virus that enters a cell from replicating. Adenoviruses, however, counteract that defensive measure by expressing their own protein, known as E1A, which binds to Rb to stop it from functioning. That allows the common cold virus to ?take hold? and spread in human cells until the immune system has a chance to destroy it.

 

The Delta-24-RGD therapy is designed to take advantage of the mutant Rb protein in cancer cells by introducing a virus with a nonfunctioning E1A protein, researchers say. Investigators created a new virus with a 24-base pair deletion in the adenovirus E1A gene so that the malfunctioning E1A protein cannot stop Rb from functioning, allowing the virus to infect and kill only cancer cells. A healthy cell with a normal Rb protein can successfully defend itself against the virus, researchers say."

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