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Genetically Modified Virus May Help Treat Brain Tumors: Study

Posted on: Saturday, 9 April 2005, 09:00 CDT

Genetically modified virus may help treat brain tumors: study

LOS ANGELES, April 8 (Xinhua) -- A virus genetically modified to kill cancer cells can significantly increase the survival of mice with an incurable human brain tumor, even in some animals with advanced disease, US researchers said on Friday.

Scientists believe this herpes simplex virus can in the future treat cancer more effectively and safely. But from animal studies to human tests may be a very long process, especially for a treatment using viruses, they noted.

The study, published in the latest issue of the journal Cancer Research, used the virus known as oncolytic virus that infects and reproduces only in malignant glioma cells and kills them. The altered virus leaves normal tissues unharmed.

According to Antonio Chiocca, a professor at Ohio State University Medical Center who led the study, the treatment extended the animals' lives by several days. If a proportional increase is achieved in humans with malignant glioma, that will be a very significant advance.

Malignant gliomas are cancers in the brain that progress quickly after diagnosis. They are nearly always fatal. After being treated with surgery, chemotherapy and radiation, the patients' average survival following diagnosis is no longer than one year.

The study began with a laboratory version of a herpes virus that was missing several genes. The virus could infect only malignant glioma cells, but once inside the cells, it replicated poorly. Therefore the virus had only a weak ability to kill cancer cells and shrink tumors.

For this study, the researchers restored the virus' ability to replicate at high levels by returning one of the genes that had been removed from the virus. First, the researchers modified the gene known as ICP34.5, so that it would be active only in cells that made a protein called nestin.

Usually, nestin is absent from cells except during embryonic development. But malignant glioma cells begin producing nestin again. This sets the cancer cells apart from normal cells and gave the researchers the trigger they needed.

In tests with laboratory-grown malignant glioma cells, the researchers found that the ICP34.5 viruses could again replicate at high levels. Then they tested the virus in mice with implanted human gliomas.

In one set of experiments, the researchers injected the virus into the mice early, seven days after implanting the tumors. Untreated mice lived for 21 days after tumor implantation. Eight of 10 mice treated with the ICP34.5 virus survived 90 days after implantation. Two of 10 mice treated with a control virus survived 90 days.

The control virus was very similar to a type used in clinical trials testing viral treatment of malignant glioma. It was similar to the experimental virus but lacking the ICP34.5 gene.

However, human glioma patients are usually diagnosed and treated later in the disease, after symptoms begin. Therefore the researchers conducted an experiment that simulated this condition.

They injected the virus into tumors 19 days after implantation and when the mice began showing symptoms, which is similar to the case in human treatment.

In this experiment, two of 10 animals treated with the ICP34.5 virus survived 24 days after implantation. Of mice treated with the control virus, all 10 died by day 21, a statistically significant difference.

Source: Xinhua News Agency - CEIS

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