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(Ivanhoe Newswire) -- Researchers have identified a protein released by dying brain tumor cells that provides an effective way to gauge the effectiveness of a novel gene therapy treatment for brain cancer. The finding paves the way for a Phase 1 clinical trial expected to begin in late 2009.
The two-pronged gene therapy was devised by scientists at the Cedars-Sinai Board of Governors Gene Therapeutics Research Institute. It uses a harmless, genetically engineered virus to deliver a combination of proteins and a drug to kill tumor cells, which triggers an ongoing immune response, thus preventing the development of recurrent malignant brain tumor cells.
The Cedars-Sinai team, led by Pedro R. Lowenstein, M.D., Ph.D., director of the Board of Governors Gene Therapeutics Research Institute, and Maria G. Castro, Ph.D., co-director of the Institute, developed this gene therapy strategy during ten years of laboratory research.
Using this therapy, we have shrunk and completely eliminated very large brain tumors in animals and have trained their immune systems to develop memory so that recurrent tumors are also destroyed, Dr. Castro, principal investigator of the study, is quoted as saying. The biomarker identified in this study will help us determine the effectiveness of the therapy in patients with glioblastoma multiforme.
In this study, researchers found that a protein released by dying tumor, called high mobility group box 1 (HMGB1), regulates gene expression in healthy cells by binding to the cells DNA. When cancerous cells are killed, however, HMGB1 is released into the general blood circulation. Measuring the levels of HMGB1 in the blood could be a non-invasive way to monitor the effectiveness of cancer treatment in patients.
Traditional treatments have little impact on patients with glioblastoma multiforme, the most common malignancy in the brain, diagnosed in about 18,000 people in the United States every year.
The immune system is considered a potential ally, but the brain has few dendritic cells -- key sentries of the immune system that detect foreign proteins and provide the initial signals for the T cells to mount an anti-tumor immune attack. Without the surveillance of dendritic cells, brain tumors go undetected and proliferate rapidly.
In the technique devised by Castro and Lowenstein, one of the proteins attracts dendritic cells from bone marrow into the tumor while another protein and the antiviral drug gancyclovir combine to kill tumor cells. The dying tumor cells are detected by the newly recruited dendritic cells, which initiate the anti-tumor response.
SOURCE: Clinical Cancer Research, July 1, 2009
This article was reported by Ivanhoe.com, who offers Medical Alerts by e-mail every day of the week. To subscribe, go to: http://www.ivanhoe.com/newsalert/.
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