R&D News: Dendritic cell vaccine may increase median survival time
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 research that a subset of patients more likely to respond to an immunotherapy has been identified, said the study's senior author, Linda Liau, a Jonsson Cancer Center researcher and a professor of neurosurgery.
The study found that the vaccine, administered after conventional 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, which was launched in 2003. Of those, about one-third are still alive, some more than eight years after their diagnosis.
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.
â€œThis is quite an encouraging result, especially in an early-phase study like this,â€ Ms Liau said. â€œIt's promising to see patients with this type of brain cancer experience such long survivals.â€
However, Ms 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 in California.
The vaccine preparation is personalized for each individual. After the tumor is removed, Ms Liau and her team extract the proteins, which provide the antigens for the vaccine to target. After radiation and chemotherapy, the white blood cells are taken from the patient and grown into dendritic cells, a type of white blood cell that is an antigen-presenting cell.
The vaccine preparation from this point takes about two weeks, as the dendritic cells are grown together with the patient's own tumor antigens. The tumor-pulsed dendritic cells are then injected back in to the body, prompting the T cells to go after the tumor proteins and fight the malignant cells.
â€œThe body may have trouble fighting cancer because the immune system doesn't recognize it as a foreign invader,â€ Ms Liau said. â€œThe dendritic cells activate the patient's T cells to attack the tumor, basically teaching the immune system to respond to the tumor.â€
The individualized vaccine is injected into the patient in three shots given every two weeks for a total of six weeks. Booster shots are given once every three months until the cancer recurs. Patients are scanned every two months to monitor for disease recurrence, Ms Liau said.
It has recently been discovered that there are at least three subtypes of glioblastoma: proneural, proliferative and mesenchymal. During the course of her study, Ms Liau and her colleagues saw that one group of patients seemed to be responding very well to the vaccine.
The researchers examined their tumors using a microarray analysis of their DNA and found that those with a gene expression profile identifying their cancers as mesenchymal responded better to the vaccine.
The finding was surprising, Ms Liau said, because patients with the mesenchymal subtype generally have more aggressive disease and shorter survival times 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. Ms Liau speculates that the vaccine helped replenish the immune system, allowing that subset of patients to more easily fight the brain cancer.
â€œGlioblastoma remains one of the diseases for which there is no curative therapy ... and the prognosis for patients with primary malignant brain tumors remains dismal,â€ the study states. â€œOur results suggest that the mesenchymal gene expression profile may identify an immunogenic sub-group of glioblastoma that may be more responsive to immune-based therapies.â€
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