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Study identifies biomarker that safely monitors tumor response to new brain cancer treatment
July 01, 2009A specific biomarker, a protein released by dying tumor cells, has been identified as an effective tool in an animal model to gauge the response to a novel gene therapy treatment for glioblastoma mulitforme. The finding, reported in the July 1 issue of Clinical Cancer Research, paves the way for a Phase 1 clinical trial expected to begin in late 2009.
The gene therapy is a two-pronged strategy devised by scientists at the Cedars-Sinai Board of Governors Gene Therapeutics Research Institute. It uses a genetically engineered, harmless virus to deliver a combination of proteins and a drug to kill tumor cells, which triggers an ongoing immune response against malignant brain tumors 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 10 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," said Castro, principal investigator of the study. "The biomarker identified in this study will help us determine the effectiveness of the therapy in patients with glioblastoma multiforme."
In this study, the researchers identified the most effective and least toxic combination of therapeutic agents that would offer the best results. They found that a protein released by dying tumor cells may be used as a "biomarker" to gauge the effectiveness of treatment. This protein, 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. This research shows that measuring the levels of HMGB1 in the blood could be a non-invasive but essential way to monitor the effectiveness of cancer therapeutics in patients. These findings will be used to fine-tune the therapy as it enters the Phase I clinical trial.
Traditional treatments have little impact on long-term survival of 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 very 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 (the immune stimulatory cytokine Flt3L) attracts dendritic cells from bone marrow into the tumor while another protein (thymidine kinase) 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. The biomarker identified in this study is a result of the ongoing battle between the T cells and the tumor cells. As such, the biomarker will be a useful direct reporter of the ensuing fight to kill the tumor.
Cedars-Sinai Medical Center
"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," said Castro, principal investigator of the study. "The biomarker identified in this study will help us determine the effectiveness of the therapy in patients with glioblastoma multiforme."
In this study, the researchers identified the most effective and least toxic combination of therapeutic agents that would offer the best results. They found that a protein released by dying tumor cells may be used as a "biomarker" to gauge the effectiveness of treatment. This protein, 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. This research shows that measuring the levels of HMGB1 in the blood could be a non-invasive but essential way to monitor the effectiveness of cancer therapeutics in patients. These findings will be used to fine-tune the therapy as it enters the Phase I clinical trial.
Traditional treatments have little impact on long-term survival of 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 very 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 (the immune stimulatory cytokine Flt3L) attracts dendritic cells from bone marrow into the tumor while another protein (thymidine kinase) 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. The biomarker identified in this study is a result of the ongoing battle between the T cells and the tumor cells. As such, the biomarker will be a useful direct reporter of the ensuing fight to kill the tumor.
Cedars-Sinai Medical Center
Tumor Cells Current Events and Tumor Cells News RSSNew Notre Dame study provides insights into the molecular basis of tumor cell behavior
A new study by a team of researchers led by Crislyn D'Souza-Schorey, associate professor of biological sciences at the University of Notre Dame, sheds light on the molecular basis by which tumor cells modulate their surroundings to favor cancer progression.
Immune therapy can protect against or treat later lymphoma
Specially developed immune system cells that target the common Epstein-Barr virus can protect immune-suppressed bone marrow transplant recipients against lymph system disease and cancers that arise from the viral infection.
Study reveals a 'missing link' in immune response to disease
The immune system's T cells have the unique responsibilities of being both jury and executioner. They examine other cells for signs of disease, including cancers or infections, and, if such evidence is found, rid them from the body. Precisely how T cells shift so swiftly from one role to another, however, has been a mystery.
Discovery offers potential new pancreatic cancer treatment
Tiny particles that can carry drugs and target cancer cells may offer treatment hope for those suffering with pancreatic cancer. New research to be presented in November at the American Association of Pharmaceutical Scientists (AAPS) Annual Meeting in Los Angeles reveals that tumor-penetrating microparticles (TPM) have been specifically designed to break through hard-to-infiltrate barriers and deliver drugs more effectively and efficiently than the standard form of chemotherapy such as those injected through a vein.
A Potential Anti-cancer Agent
Pateamine A (PatA), a natural product first isolated from marine sponges, has attracted considerable attention as a potential anti-cancer agent, and now a new activity has been found for it, which may reveal yet another anti-cancer mechanism.
Immunotherapy demonstrates long-term success in treating lymphoma
Targeted immunotherapy has been an attractive new therapeutic area for a number of cancers because it has the potential to destroy tumor cells without damaging surrounding normal tissue. New study results demonstrate high success rates using specialized white blood cells to prevent or treat lymphoma associated with the Epstein-Barr virus (EBV-lymphoma) in patients who have received a hematopoietic stem cell transplant (HSCT).
Duke develops nano-scale drug delivery for chemotherapy
Going smaller could bring better results, especially when it comes to cancer-fighting drugs.
Researchers use drug-radiation combo to eradicate lung cancer
Researchers at UT Southwestern Medical Center have eliminated non-small cell lung (NSCL) cancer in mice by using an investigative drug called BEZ235 in combination with low-dose radiation.
Inhibitor of heat shock protein is a potential anticancer drug, Penn study finds
Like yoga for office drones, cells do have coping strategies for stress. Heat, lack of nutrients, oxygen radicals - all can wreak havoc on the delicate internal components of a cell, potentially damaging it beyond repair.
Alcohol activates cellular changes that make tumor cells spread
Alcohol consumption has long been linked to cancer and its spread, but the underlying mechanism has never been clear.
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