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A double-barreled immune cell approach for neuroblastoma
November 03, 2008Adding an artificial tumor-specific receptor to immune system cells called T-lymphocytes that target a particular virus extended and improved the cells' ability to fight a form of childhood cancer called neuroblastoma, said researchers form Baylor College of Medicine and Texas Children's Hospital in a report that appears online today in the journal Nature Medicine.
"This is a way to convert a naturally occurring problem into a benefit in treating cancer," said Dr. Malcolm Brenner, director of the Center for Cell and Gene Therapy at BCM, TCH and The Methodist Hospital, and professor of pediatrics and medicine at BCM. He and his colleagues reported on using the new treatment in 11 patients with recurring neuroblastoma. "For the first time, we started to see tumor responses. We have one complete remission and others who have had stable disease for more than a year," said Brenner.
The patients responded after only the one infusion of cells because they last a long time in the body and their numbers can increase, said Brenner.
Previous attempted to use T-lymphocytes with an artificial receptor directed to tumor cells proved disappointing because they disappeared from the body too quickly to have an anti-cancer effect. However, cytotoxic T cells that already have a natural receptor for the Epstein-Barr virus are continually activated by the presence of the virus, which is never eliminated from the body.
Brenner and his group added to these T-lymphocytes a particular receptor for a protein called diasialoganglioside GD2, which is found in human neuroblastoma cells.
"We took the T-lymphocytes' with specificity for Epstein-Barr and added another receptor," said Brenner. "In effect they trampoline off the virus and onto the tumor."
Thus these cytotoxic T-lymphocytes remain in the body because they are constantly stimulated by the virus. Their artificial antigen receptor enables them to latch onto and kill the cancer cells.
When the researchers put the artificial receptor into both ordinary T-lymphocytes and those that are stimulated by the virus into the 11 patients, they found that the cancer directed cells stimulated by the Epstein-Barr virus lasted as long as 18 months and at higher levels than the other cells.
Neuroblastoma is a tumor of primitive cells that go on to form the sympathetic nervous system. Apart from brain tumors, it is the most common solid cancer of children, and accounts for 7 percent of the total. In two-thirds of cases, it is not diagnosed until it has already spread to other parts of the body.
He and his colleagues hope to improve the treatment to make the T-lymphocytes more potent cancer killers, he said. One way would be to add specific receptors for proteins that allow the T-lymphocytes to avoid the immune-dampening effects of the cancers. Another might be to give the treatment right after the patients receive a stem cell transplant. At that time, the number of tumor cells would be at its lowest and there would be a lot of signals telling the T-lymphocytes to increase in number.
Within the next year, they plan to add receptors for other cancers to the virus-specific T-cells and see if they get the same cancer-fighting effect.
Baylor College of Medicine
Previous attempted to use T-lymphocytes with an artificial receptor directed to tumor cells proved disappointing because they disappeared from the body too quickly to have an anti-cancer effect. However, cytotoxic T cells that already have a natural receptor for the Epstein-Barr virus are continually activated by the presence of the virus, which is never eliminated from the body.
Brenner and his group added to these T-lymphocytes a particular receptor for a protein called diasialoganglioside GD2, which is found in human neuroblastoma cells.
"We took the T-lymphocytes' with specificity for Epstein-Barr and added another receptor," said Brenner. "In effect they trampoline off the virus and onto the tumor."
Thus these cytotoxic T-lymphocytes remain in the body because they are constantly stimulated by the virus. Their artificial antigen receptor enables them to latch onto and kill the cancer cells.
When the researchers put the artificial receptor into both ordinary T-lymphocytes and those that are stimulated by the virus into the 11 patients, they found that the cancer directed cells stimulated by the Epstein-Barr virus lasted as long as 18 months and at higher levels than the other cells.
Neuroblastoma is a tumor of primitive cells that go on to form the sympathetic nervous system. Apart from brain tumors, it is the most common solid cancer of children, and accounts for 7 percent of the total. In two-thirds of cases, it is not diagnosed until it has already spread to other parts of the body.
He and his colleagues hope to improve the treatment to make the T-lymphocytes more potent cancer killers, he said. One way would be to add specific receptors for proteins that allow the T-lymphocytes to avoid the immune-dampening effects of the cancers. Another might be to give the treatment right after the patients receive a stem cell transplant. At that time, the number of tumor cells would be at its lowest and there would be a lot of signals telling the T-lymphocytes to increase in number.
Within the next year, they plan to add receptors for other cancers to the virus-specific T-cells and see if they get the same cancer-fighting effect.
Baylor College of Medicine
Neuroblastoma Current Events and Neuroblastoma News RSSWeizmann Institute Scientists Discover A New Protein Partnership That Leads to Pediatric Tumor Regression
Why are some pediatric cancers able to spontaneously regress? Prof. Michael Fainzilber and his team of the Weizmann Institute's Biological Chemistry Department seem to have unexpectedly found part of the answer.
PET Can Help Guide Treatment Decisions for a Common Pediatric Cancer
A new study published in the August issue of The Journal of Nuclear Medicine shows that positron emission tomography (PET) is an important tool for depicting the extent of neuroblastoma in some patients, particularly for those in the early stages of the disease.
Protein That Promotes Cancer Cell Growth Identified
Scientists at Burnham Institute for Medical Research (Burnham) have found that the Caspase-8 protein, long known to play a major role in promoting programmed cell death (apoptosis), helps relay signals that can cause cancer cells to proliferate, migrate and invade surrounding tissues.
U of M Researchers Find Childhood Cancer Risk Rises with Mother's Age
Research from the Masonic Cancer Center, University of Minnesota indicates that a baby born to an older mother may have a slightly increased risk for many of the cancers that occur during childhood.
Variations in 5 genes raise risk for most common brain tumors
Common genetic variations spread across five genes raise a person's risk of developing the most frequent type of brain tumor, an international research team reports online in Nature Genetics.
Genetic finding could lead to targeted therapy for neuroblastoma
Researchers have identified a genetic glitch that could lead to development of neuroblastoma, a deadly form of cancer that typically strikes children under 2.
Researchers identify gene that regulates tumors in neuroblastoma
Virginia Commonwealth University researchers have identified a gene that may play a key role in regulating tumor progression in neuroblastoma, a form of cancer usually found in young children.
New therapy enlists immune system to boost cure rate in a childhood cancer
A multicenter research team has announced encouraging results for an experimental therapy using elements of the body's immune system to improve cure rates for children with neuroblastoma, a challenging cancer of the nervous system.
Immunotherapy effective against neuroblastoma in children
A phase III study has shown that adding an antibody-based therapy that harnesses the body's immune system resulted in a 20 percent increase in the number of children living disease-free for at least two years with neuroblastoma.
Drug therapy reduces neuroblastoma tumor growth in pre-clinical investigation
Researchers from the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center have discovered a new drug combination that significantly hinders tumor growth in neuroblastoma, a childhood cancer.
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