Despite aggressive treatment, glioblastoma multiforme (GBM) – the most common and deadly of brain cancers – usually claims the lives of its victims within six to 12 months of diagnosis. This statistic has changed little over the years, largely because the cancer grows so quickly that neither surgery, radiation, or chemotherapy can stop it.
Now, researchers at Cedars-Sinai Medical Center have found that a small protein called hsFlt3L delivered via a genetically engineered virus increased the number of immune cells in the brain and significantly slowed tumor growth, increasing the survival of laboratory rats in pre-clinical studies. The study, published in the December issue of the journal, Molecular Therapy, may lead to a new way to treat patients with GBM. "Importantly, our study is the first to show that GBM tumors shrank or were completely eliminated in lab rats, which is likely due to the ability of the protein, hsFlt3L to stimulate the production of fully mature immune cells within the brain," said Maria Castro, Ph.D., co-director of the Gene Therapeutics Research Institute at Cedars-Sinai Medical Center and the senior author of the study. "Since gene therapy has given us the tool to deliver this protein, our hope is to translate these laboratory studies into clinical trials in patients with GBM."
GBM tumors develop in the supportive tissue of the brain and grow quickly, often becoming very large before a person experiences symptoms and is diagnosed. Surgery is typically performed to remove as much of the tumor as possible and followed with radiation and/or chemotherapy to slow progression of the disease. But despite aggressive treatment, the tumor recurs and patients usually die within a years time. Because GBM is so aggressive, the disease has been the target of a number of laboratory studies and clinical trials investigating the effectiveness of gene therapy to deliver novel therapeutic agents to the brain. Most of these have investigated the use of the suicide gene from the herpes simplex virus to develop a gene therapy approach that kills cancer cells, in the presence of the antiviral drug, gancyclovir. In laboratory studies, this type of gene therapy has proved almost 100 percent effective. But in clinical trials, it has had limited effectiveness, suggesting that the virus is not able to deliver the suicide gene effectively into a large tumor mass. "Importantly, results from these studies showed us that gene therapy was safe, but that we needed to design a viral vector that would harness the power of the immune system to help eliminate the tumor," commented Dr. Castro.
Kelli Hanley | EurekAlert!
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