A dendritic cell vaccine personalized for each individual based on the patient's own tumor may increase median survival time in those with a deadly form of brain cancer called glioblastoma, an early phase study at UCLA's Jonsson Comprehensive Cancer Center has found.
Published this week in the peer-reviewed journal Clinical Cancer Research, the study also identified a subset of patients more likely to respond to the vaccine, those with a subtype of glioblastoma known as mesenchymal, which accounts for about one-third of all cases. This is the first time in brain cancer that a subset of patients more likely to respond to an immunotherapy has been identified, said Dr. Linda Liau, a Jonsson Cancer Center researcher, professor of neurosurgery and senior author of the study.
The study found that the vaccine, administered after the conventional treatments of surgery and radio-chemotherapy, was associated with a median survival of 31.4 months, double the 15 months of historical controls in the published literature. In all, 23 patients were enrolled in the Phase I study that was launched in 2003. Of those, about one third of participants are still alive, some more than eight years after their diagnosis.
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The study also found that the vaccine was safe and that side effects were minimal, limited mostly to flu-like symptoms and rashes near the vaccine injection site.
"This is quite an encouraging result, especially in an early phase study like this," Liau said. "It's promising to see patients with this type of brain cancer experience such long survivals."
However, Liau cautioned that the findings need to be confirmed in larger, randomized studies. She currently is leading a Phase II, randomized study at UCLA testing the vaccine in newly diagnosed glioblastoma patients. The patients will receive either the standard of care (surgery, radiation and chemotherapy) or the standard of care plus the vaccine. The study is a multi-center trial, and UCLA is the only site offering it in California.
It has recently been discovered that there are at least three subtypes of glioblastoma: proneural, proliferative and mesenchymal. During the course of her study, Liau and her colleagues saw that one group of patients seemed to be responding very well to the vaccine and examined their tumors using a microarray analysis of their DNA. They found that those with a gene expression profile identifying their cancers as mesenchymal responded better to the vaccine.
The finding was surprising, Liau said, because patients with the mesenchymal subtype generally have more aggressive disease and shorter survival than those with the other subtypes. In patients with this type of glioblastoma, several genes that modulate the immune system are dysregulated, meaning they don't work properly. Liau speculates that the vaccine helped replenish the immune system, allowing that subset of patients to more easily fight the brain cancer.
