Anticancer Genes Planted into Normal Brain Tissues Eliminate Nearby Tumors

In recent years, attempts have been made to treat this disease by gene therapy, the introduction of various types of toxic genes directly into the tumor. However, this technique has proven unsuccessful because it has not been possible to insert the genes into 100% of the tumor cells. Following the death of the transfected cells, surviving tumor cells are free to grow and spread. Repeated injections of anti-cancer genes generally stimulate production of antibodies that render the treatment ineffective.
Investigators at Massachusetts General Hospital (Charlestown, MA, USA) have taken a different approach. They reasoned that by injecting the gene for the anti-cancer protein INF-beta into the normal tissues surrounding the tumor, they would create a barrier preventing the tumor from spreading. Eventually the INF-beta secreted by the nearby tissues would destroy the tumor itself.

Results published in the October 2008 issue of the journal Molecular Therapy showed that this method could work. They showed that a single injection of adeno-associated virus (AAV) vector encoding IFN-beta caused significant shrinkage of brain tumors in a mouse model within four days. After two weeks, the tumors disappeared completely.

Since interferon-beta treatment is known to have side effects, it will be necessary to identify any toxicity caused by long-term secretion of the protein in the brain and develop preventive strategies, such as turning off the introduced genes.

"These results are particularly important as we build on our understanding of the microenvironments that allow tumors to grow and spread,” explained senior author Dr. Miguel Sena-Esteves, assistant professor of neurology at Massachusetts General Hospital. "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. 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.”

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