October 10, 2008
New approach may shrink brain tumors

MGH researchers are investigating a new approach to gene therapy for brain tumors –  delivering a cancer-fighting gene to normal brain tissue around the tumor to keep it from spreading. An animal study published in the journal Molecular Therapy found that inducing mouse brain cells to secrete human interferon-beta – a protein being tested against several types of cancer –  suppressed and eliminated growth of human glioblastoma cells implanted nearby.

"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," says Miguel Sena-Esteves, PhD, of the MGH Neuroscience Center, the study's senior author. "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."

Clinical trials of gene therapies for glioblastoma – the most common and deadly form of brain tumor – have been disappointing. Several factors have made it difficult to deliver cancer-eliminating genes throughout tumors, and when tumor cells have been induced to produce an anticancer protein, levels of that protein drop as the tumor dies, allowing remaining tumor cells to resume growing. To test whether expressing a therapeutic gene in normal brain cells could form that zone of resistance, the MGH researchers delivered a gene for human interferon-beta into the brains of immune-deficient mice using viral vectors that do not induce an immune reaction. 

Two weeks later, human glioblastoma cells were injected into the same areas of the animals' brains. After only four days, tumors growing in mice expressing interferon-beta were significantly smaller than tumors in a control group.  Two weeks later, the tumors had completely disappeared from the brains of the gene-therapy-treated mice. 

"These results are particularly important as we build on our understanding of the microenvironments that allow brain tumors and other types of cancer to grow and spread," explains Sena-Esteves. "The ability to genetically engineer normal tissue could manipulate that microenvironment, preventing tumors from migrating within a patient's brain and escaping other therapies." 

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