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Title : Can this deadly virus kill cancer? Scientists experiment
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Can this deadly virus kill cancer? Scientists experiment

this deadly virus can kill cancer? Scientists experiment

People faces one of the most feared diagnoses of medicine may one day have little hope a source :. Injections to treat some types of brain cancer from a deadly tropical virus

can this deadly virus kill cancer: scientific experiments (image courtesy of: Anthony N. Van den Pol)

the virus, called Lassa, is the cause of hemorrhagic fever endemic in West Africa particularly unpleasant. The research sounds scary, but a team of Yale and Harvard is using part of the genetic code of Lassa virus to other safe enough to be injected into the human brain, where it will hunt down and kill cancer cells.

Lassa partner in this mission is to search and destroy the vesicular stomatitis virus, or VSV. Most people who contract never get sick, and those who do usually only have flu-like symptoms. But if the brain is infected, VSV becomes mortal. Ironically, it is the scariest of Lassa makes sure the generally harmless VSV for use in this delicate organ.


Some VSV virus, including, are good to attack cancer cells without infecting healthy cells nearby. Many types of cancer cells are vulnerable to certain viruses, including VSV, because they can not produce interferon, a protein that normal cells used to fight infection. Some researchers believe that these viruses as the solution to one of its biggest challenges :. Kill the cancer without harming the patient

The researchers tested VSV against various cancers in laboratory experiments, and usually is effective without harming healthy cells. A team from the Mayo Clinic initiated a clinical trial in 2012 to test VSV against liver cancer; It is still ongoing. "We have been working with VSV for a number of years, and VSV has always been a very good virus to infect cancer cells," said Anthony van den Pol, professor of neurosurgery at Yale whose team has tested VSV against cancer in animals laboratory and in human cell cultures. "But the problem has always been that if VSV gets into the brain, can cause neurological problems or even death."

In the brains of laboratory mice and in cultured human brain cells, VSV attacks the cancer, but it also kills healthy brain cells. It seems that the VSV glycoprotein - a protein on the outer surface of the virus that engages into host cells - neurons joins too easily. Once that happens, the virus takes over the cell and uses the internal structures of the cell to produce new copies of the virus. Over time, the infected cell will burst, scattering particles like shrapnel virus to attack neighboring cells.



despite the long queues neurons, called axons, carry nerve impulses throughout the body, their body, or soma, are found mainly in the brain and spinal cord . Usually it is safe to use VSV cancer in most parts of the body, due to a barrier usually keeps the virus in the blood reaches the brain and spinal cord, but it is too dangerous to use the virus against brain cancer.

glycoprotein Each virus has a different shape, so Van den Pol and his team thought that if they could replace the VSV glycoprotein with another virus might be safe enough for use in the brain. The list of candidates was a roll of terrifying viral diseases: Ebola, Marburg, the lymphocytic choriomeningitis virus (LCMV), rabies and Lassa. These five viruses have glycoproteins that, like the VSV glycoprotein, would join a wide range of cell types, so the researchers believe there is a good chance that also bind to various types of cancer.

Van den Pol and his colleagues do not work with live samples; Rather, sections of genetic material of each virus used. The team eliminated the gene encoding the VSV glycoprotein and replaced with a gene coding for virus glycoprotein another. When the computer made, which had five new viruses, man-made. Of the five, the most effective was Lassa-VSV.

Lassa virus-VSV is a chimera, an organism that is created by combining two different genomes of organisms to make something new. It kills brain tumors without harming healthy neurons, apparently because it can bind to normal cells, but does not actually infect them.

"We believe that normal cells are able to block replication of the virus and the virus does not get a foothold," said Van den Pol. The team published its findings in the journal Journal of Virology.



Virus cancer the researchers tested their chimeras against some of the deadliest forms of brain cancer. Glioma can kill people within a year. The prognosis may be even worse for patients with melanoma skin cancer if it spreads in the brain.

glioma tumor cells (in red) are being destroyed in the brain (rat) by a chimeric virus (green) containing a gene virus Lassa fever, Ebola pathogen Similary. (Courtesy of Anthony N. Van den Pol) in laboratory cultures of glioma and melanoma, Lassa, Ebola and VSV-VSV worked so well that the researchers decided to test them in mice. human glioma cells were implanted in mice forebrains. The animals that received no treatment died within approximately 29 days. The mice that received injections of Lassa-VSV were doing well 80 days later, when researchers reported their survivors. The virus is destroyed without damaging tumors brain cells. Those who received Ebola-VSV fared slightly less well but still better than those who received no treatment.

In high-grade gliomas, cancer cells often migrate within the brain. When that happens, surgery or radiation may miss a rogue group of cells, cancer leaving an additional point of support. When researchers implanted two tumors in the mouse brain, one in each hemisphere, and then injected the mice with Lassa-VSV, the virus infected and killed a tumor, and then spread through the brain to attack the second one without infecting brain cells along the way.

The next steps However, Lassa-VSV will not work every time. Each cancer is caused by a single set of mutations. Some of these mutations cause the most susceptible to Lassa-VSV tumors, but others make the cancer more difficult for the virus target.


for example, Lassa-VSV was less effective in killing laboratory cultures of a type of glioma, U118, which otherwise, U87. Other chimeras may be better able to target the virus, however. Chimera Ebola-VSV used in the study Van den Pol was effective against U118, though less than Lassa-VSV, and a 2008 study found that the LCMV-VSV Chimera also had the potential to hunt safely down brain tumors.

Successful treatment in mice does not guarantee that function in humans. "We hope that what we have learned from rodent studies can be generalized to humans, but of course there is the possibility that there is some difference in humans that could result in lower or no effectiveness of Lassa-VSV," he said van den Pol in an email.

Primate Research would usually be the next step. "The first thing we would do is inject the virus in a primate brain to be the main question 'Is this safe or not?' because if it is not safe, is the end of the road, "said Van den Pol. This test requires a clinical grade version unpolluted virus produced in a special laboratory.

It is an expensive process. "In my lab, I make a liter of clean virus for about $ 100 or $ 200, but to get a virus clinical grade would cost about a million dollars, and I just can not find the money," said Van den Pol. it can be difficult to find someone willing to finance possible treatments at this stage, he said, because there is still a chance that Lassa-VSV not work in humans. "You know, if it works, it's almost nothing, and if it fails, of course, is a big investment in anything."

Meanwhile, researchers are testing Lassa-VSV against melanoma in mice. The team is particularly interested in whether the virus can not only kill cancer cells, but also help guide the patient's immune system and destroy cancer cells.

As part of the body's immune response, T cells recognize and destroy infected cells before they can release more virus particles and spread infection. Some cancer cells produce molecules that trick the immune system ignore them, but when Lassa-VSV infects a cancer cell, which may signal the T cells and other immune system cells to attack the infected cell.

By targeting cancer cells infected with Lassa-VSV, the body's immune response can also learn to recognize and attack cancer cells long after the virus is gone. Lassa-VSV virus carries a gene that makes a fluorescent protein that helps researchers track the cells that have been infected by the virus occurs. In mice, the immune system produces antibodies to the virus not only direct but also the protein. Researchers hope that if the immune system can learn to direct a protein associated with the virus, but also could generalize from infected cancer cells all cancer cells.

If it works, it could help protect patients against relapse. "If tumor cells were to return X number of months later, the immune system still recognize the tumor as something to aim," said Van den Pol. The researchers still have much work to do to understand how immune cells within a tumor cells differ from normal.

Currently, the team is studying how Lassa-VSV works against melanoma tumors in mice, and Van den Pol said the results are promising. Mice that had Lassa-VSV injected into their tumors "have substantially smaller tumors and they are still doing pretty well right now," said Van den Pol, but added that the team is not sure yet if the immune system of the body he will take over and remove the melanoma completely or if you just keep the tumor under control, but not destroy it.



Van den Pol is optimistic about the potential of Lassa-VSV. "The fact that Lassa-VSV both glioma and melanoma targets suggests that the virus could be good in the orientation of many other cancers," he said.

By Kiona Smith-Strickland
: The Washington Post

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