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Coming Soon, a New Approach to Gene Therapy That Prevents Tumour Spread

by Rajashri on September 27, 2008 at 1:47 PM
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 Coming Soon, a New Approach to Gene Therapy That Prevents Tumour Spread

A new approach to gene therapy for brain tumors is being developed by researchers at Massachusetts General Hospital (MGH). The treatment envisages delivering a cancer-fighting gene to normal brain tissue around the tumor to keep it from spreading.

This the first study to test the feasibility of such an approach, which found that inducing mouse brain cells to secrete human interferon-beta suppressed and eliminated growth of human glioblastoma cells implanted nearby.

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"We had hypothesized that genetically engineering normal tissue surrounding a tumor could create a zone of resistance - a microenvironment that prevents the growth or spread of the tumor. This proof of principle study shows that this could be a highly effective approach, although there are many additional questions that need to be investigated," said Miguel Sena-Esteves, PhD, of the MGH Neuroscience Center, the study's senior author.

Glioblastoma is the most common and deadly form of brain tumor. Human clinical trials of other gene therapies have not significantly reduced tumor progression.
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In the current study the researchers examined whether expression of a therapeutic gene in normal brain cells could form a stable and effective anti-tumor reservoir.

The researchers first pretreated immune-deficient mice by delivering a gene for human interferon-beta - a protein being tested against several types of cancer - into the animals' brains using adeno-associated virus vectors known to effectively deliver genes to neurons in the brain without the immune reaction produced by other vectors.

After two weeks, human glioblastoma cells were injected into the same or adjacent areas of the animal's brains. Only four days later, mice expressing interferon-beta had significantly smaller tumors as compared to a control group pretreated with gene-free vector.

Two weeks after the glioblastoma cells were introduced, the tumors had completely disappeared from the brains of the gene-therapy-treated mice.

Several additional experiments verified that the anti-tumor effect was produced by expression of interferon-beta in normal tissue. The same tumor growth suppression was seen when the genes were delivered to one side of the brain and tumor cells were injected into the other.

Using a specialized vector that allows genes to be expressed only in neuronal cells and not the glial cells from which glioblastomas originate also produced similar results.

Unlike other gene therapy studies, these experiments were able to suppress growth and eliminate the implanted tumor with a single injection of the interferon-beta-encoding vector, underscoring the approach's effectiveness.

"These results are particularly important as we build on our understanding of the microenvironments that allow tumors to grow and spread. The therapeutic principle of genetically engineering normal brain tissue could be used to manipulate proteins required for that microenvironment, preventing tumors from migrating within the patients brain and escaping other therapies," explained Sena-Esteves, an assistant professor of Neurology at Harvard Medical School.

An animal study published in the journal Molecular Therapy.

Source: ANI
RAS/SK
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