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Immune Targeting of Glioblastoma Cancer Stem Cells

Last Updated: 1/29/2011

Glioblastoma multiforme, the most common and most aggressive form of primary brain tumors in humans presents a myriad of challenges, notes John S. Yu, M.D., Professor and Vice-chair, Department of Neurosurgery, Cedars-Sinai Medical Center and Chairman and CSO, Immunocellular Therapeutics, Ltd. (www.imuc.com). "Despite years of advances with glioblastoma, survival remains less than 15 months. One problem is that of cancer stem cells that infiltrate the brain as microsatellites of tumors."

Yet there is hope. Dr. Yu’s NIH funded laboratory has identified a cancer stem cell. It is like the emperor cell of the cancer that alone has the ability to make more and more helper cells. It is like the queen bee. It’s like the root of a weed that sprouts more weeds even though you think you’ve killed it. Hence, even after radiation and chemotherapy, these tumors grow back with a vengeance.

"We have developed a cancer vaccine that uses your own white cells and targets specific proteins on the cancer stem cell. Unlike a preventive vaccine like smallpox, this vaccine is given after you have the cancer. So, it’s like using the cancer to kill the cancer. We are trying to target the cancer stem cell, the emperor cell, rather than using the immune system’s energy to kill every soldier cancer cell, we are going for the jugular," Dr Yu gets animated.

Dr. Yu was fascinated by the possibility of affecting disease at its root, at the cancer stem cell level. "We have historically targeted the less important daughter cell with radiation and chemotherapy. Cancer stem cells are resistant to these forms of thereapy. I developed an interest in targeting cancer stem cells to get at the root of these tumors." To that end, Dr. Yu’s group utilized a dendritic cell vaccine strategy to target tumor specific antigens what are overexpressed on glioblastoma cancer stem cells. Dendritic cells are antigen-presenting cells that appear to play an important role in initiating immune responses and are also potent inducers of T-cell mediated responses. "We are looking to root out cancer stem cells, just as one would try to remove the root of weeds in order to get rid of them," said Dr. Yu. In pursuing cancer vaccine therapy, we are one of the first groups to identify the cancer stem cell population in glioblastomas, and we are trying to use the immune system to target these cancer stem cells. "

In the study that Dr. Yu presented, his group is using ICT-107, a dendritic cell-based vaccine that works by stimulating an immune response to antigens that are overexpressed by cancer stem cells. Through this trial sponsored by Immunocellular Therapeutics, Dr. Yu’s group is targeting 6 specific proteins in this cell population. Early results, Dr. Yu notes, are promising. "Of 17 glioblastoma patients treated in this phase 1 trial, 41 percent of patients developed an antigen specific interferon gamma response after vaccination," he noted. "The median progression free survival was over 17 months, and the median survival was not reached to date. The planned Phase II trial will enroll 102 patients who will be randomized to receive the vaccine versus a control vaccine. We hope to better identify the therapeutic potential of this vaccine in this trial." Patients will receive vaccine along with the standard of care which is radiation and temozolomide. The trial is now enrolling.. For more details on the trial, click HERE.




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