New weapons in the brain cancer fight
Date: April 30, 2012
Brain cancers, particularly gliomas, are some of the most difficult cancers to treat. Although surgery and chemotherapy are helpful, they’re typically not as effective as physicians or their patients hope for, says neurosurgeon Michael Lim.
“Especially for gliomas, these therapies offer incremental benefits, but no cures,” he explains. “Novel therapies are badly needed.”
Taking steps toward that goal, Lim says, Johns Hopkins is on track to begin three clinical trials for glioma vaccines. It also recently began using CyberKnife, a frameless radiotherapy system that provides a more comfortable treatment option for patients with glioma and other brain cancers.
The first trial involves a vaccine based on heat shock protein, which is normally present only inside cells. When this protein is present outside of cells—a scenario that occurs when cells are dead or damaged—it’s a vigorous activator of the immune response, which organizes its army of cells to clean up the debris.
Using this natural response to their own advantage, Lim explains, researchers have developed a vaccine that links proteins from patients’ own glioma tumors to this heat shock protein. As a result, the immune system learns to identify tumor-specific proteins that are isolated individually from each patient, thereby creating a personalized vaccine.
“When it’s turned on by the heat shock protein,” Lim says, “the immune system also sees the cancer proteins and learns what it needs to fight.”
The second trial will use a vaccine based on dendritic cells.
Several previous dendritic cell vaccines, typically formulated by mixing portions of a tumor with the patient’s own dendritic cells, haven’t been successful, Lim says, because the portion of tumor used for the vaccine sometimes isn’t representative of the entire tumor, leading to an incomplete immune response. To get around this problem, researchers taught dendritic cells how to recognize six commonly expressed proteins on gliomas.
“Rather than using the tumor itself, we’re exposing dendritic cells to just the common tumor proteins,” Lim says.
The third vaccine is only for a small subset of glioma patients—about 20 percent—whose tumors express a protein called epidermal growth factor receptor variant 3, or EGFRvIII, a protein originally discovered by Johns Hopkins researcher Bert Vogelstein and his postdoctoral fellow, Albert Wong, now a professor at Stanford University. By giving patients a vaccine with this protein, linked to an immunostimulant, researchers are looking for the immune system to fight cells expressing EGFRvIII.
Complementing these efforts is Hopkins’ CyberKnife. Much like the Gamma Knife, another technology that Hopkins had been using for years, this new machine aims beams of radiation at patients’ tumors. It can also be used to treat other conditions, such as arteriovenous malformation and trigeminal neuralgia. However, it comes with an additional benefit for patients. While Gamma Knife requires that patients’ heads be fixed into a stereotactic frame, CyberKnife allows frameless treatment. The radiation beams adjust to continue treating a tumor, even if a patient’s head moves.
“We’re ensuring that patients get the best and newest technology,” Lim says, “while also minimizing any discomfort.”
The result is a full range of treatments that includes new ways to extend and improve brain cancer patients’ lives.
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