Investigators at the UCLA Health Jonsson Comprehensive Cancer Center have pinpointed a combination immunotherapy treatment that enhances the immune response for people with malignant gliomas, an aggressive type of brain tumor that is fast growing and difficult to treat.
The study, published in Nature Communications, found that pairing a personalized dendritic cell vaccine with the immune-boosting substance poly-ICLC enhances the immune response and activity of T cells in patients with malignant glioma, and improves the dendritic cells’ ability to fight the brain tumor more effectively than the vaccine alone.
“Treating malignant gliomas is very complex and due to the infiltrative nature of these tumors and their location in the brain, these patients often have a poor prognosis,” said Robert Prins, a professor of molecular and medical pharmacology and of neurosurgery at the David Geffen School of Medicine at UCLA, and co-senior author of the study. “By improving the potency of the vaccine, we’re hoping it can induce more effective anti-tumor immune responses in patients diagnosed with malignant gliomas.”
The dendritic cell vaccine, pioneered at UCLA, uses a person’s own white blood cells to help activate the immune system to fight cancer. Dendritic cells typically alert the immune system when it detects a foreign invader.
The vaccine works by combining brain tumor protein antigens derived from surgically removed tumors with dendritic immune cells generated from the patient’s own blood. The dendritic cells train the immune system to recognize the tumor antigens so that when they are injected back into the patient the immune system will be educated to recognize and attack tumor cells.
While the vaccine has shown promise in treating patients with malignant gliomas, the treatment does not work for everyone.
To further amplify the anti-tumor immune response, researchers looked at adding toll-like receptor (TLR) agonists to the vaccine. TLR agonists bind and activate a family of evolutionarily conserved receptors expressed by dendritic cells and macrophages to help alert the immune system to foreign pathogens. By activating these TLRs on dendritic cells, the UCLA team theorized that the combination might then increase the frequency and infiltration of antitumor specific T cells, while reducing the suppressive capacity of the tumor microenvironment.
AANS Neurosurgeon is the official socioeconomic publication of the American Association of Neurological Surgeons (AANS) and features information and analysis for contemporary neurosurgical practice. Published monthly online, AANS Neurosurgeon focuses on issues related to neurosurgery legislation, the workforce and practice management.
