A vaccine created by scientists at Cedars-Sinai produced an immune response in some patients against a deadly brain cancer known as glioblastoma and may have prolonged patients' lives. The results are published in the peer-reviewed journal Clinical Cancer Research.
A vaccine created by Cedars-Sinai scientists produced an immune response against a deadly brain cancer. (Illustration by Getty Images.)
Glioblastomas grow and spread extremely quickly. They are powered by small numbers of cancerous stem cells that are resistant to radiation therapy and chemotherapy. This resistance makes glioblastoma one of the most lethal cancers.
"What we're trying to do is guide the immune system to kill cancer stem cells," said John S. Yu, MD, vice chair of neurosurgical oncology in the Department of Neurosurgery at Cedars-Sinai and corresponding author of the new study.
The trial evaluated 36 people with glioblastomas and sought to determine whether the vaccine was safe. In nine patients, blood tests showed their bodies created immune system cells known as T cells that could potentially attack cancerous stem cells in the brain. On average, these patients lived for 20 months—longer than the average time of 14.6 months for people with glioblastoma.
Prior to enrolling, the study participants underwent surgery to have their brain tumors removed. The investigators then withdrew blood from each person. They extracted white blood cells and converted them into dendritic cells, which tell the immune system when there is a foreign or diseased cell in the body.
John S. Yu, MD
Yu and colleagues also isolated cancer stem cells from one patient's tumor and grew these cells in a laboratory. The investigators added proteins from the cancer stem cells to the dendritic cells. The investigators hypothesized that by injecting these dendritic cells under the skin of study participants, the cells would migrate to the lymph nodes, the tiny structures throughout our bodies that contain T cells. Once there, the dendritic cells would direct the T cells to fight the cancer stem cells bearing these proteins.
"Our hope was the dendritic cells would teach the T cells to go after the glioblastoma cancer stem cells, just like a hound dog would go after a criminal after having been given the scent of a criminal's clothes," said Yu, a professor of Neurosurgery.
Study participants received a weekly dose of the vaccine for four weeks and then once every eight weeks until they used all of the allotted vaccine or their condition worsened. The vaccine was shown to be safe and only caused minor side effects such as fever, injection site reaction, fatigue and muscle aches.
"The main takeaway is that we can generate an immune response against cancer stem cells, which is very encouraging," Yu said. "That appears to translate into a survival benefit, but we have to do larger studies to determine the degree of benefit."
This study builds upon previous research showing vaccines may teach the body to fight brain cancer. Other studies have used different types of cells to get the body to unleash an immune response.
"It will require a synergy of several approaches to mount a potent enough response to show an obvious benefit," Yu said. "I'm hopeful that in my lifetime we will make a dramatic impact on the survival of people with glioblastoma."
Funding: Research reported in this study was supported by a National Cancer Institute grant under award number NCT02010606.
