We've updated our Privacy Policy to make it clearer how we use your personal data. We use cookies to provide you with a better experience. You can read our Cookie Policy here.

Advertisement

New Brain Tumor Therapy Helps Immune System Recognize Cancer Cells

Cancer cells.
Credit: iStock.
Listen with
Speechify
0:00
Register for free to listen to this article
Thank you. Listen to this article using the player above.

Want to listen to this article for FREE?

Complete the form below to unlock access to ALL audio articles.

Read time: 2 minutes

In a major advance for the treatment of the deadly brain cancer glioblastoma, Northwestern Medicine scientists used ultrasound technology to penetrate the blood-brain barrier and provide a small dose of a chemotherapy and immunotherapy drug cocktail. The study, published in Nature Communications, found that this treatment boosted the immune system’s recognition of the cancer cells and could lead to a new treatment approach.


The scientists made several breakthroughs reported in a new study, including showing for the first time that a skull-implantable ultrasound device can enhance the penetration of the chemotherapy drug doxorubicin and immune checkpoint blockade antibodies — a novel immunotherapy treatment combination — into the human brain. The device produces microbubbles that temporarily open the blood-brain barrier, allowing the immunotherapy to enter the brain.


The scientists also showed for the first time that a small dose of doxorubicin (smaller than the dose used for traditional chemotherapy regimens) delivered with the immune checkpoint antibodies can boost the recognition of malignant glioblastoma cells by the immune system and reinvigorate the lymphocytes (immune cells) that are in charge of attacking the cancer cells.

Want more breaking news?

Subscribe to Technology Networks’ daily newsletter, delivering breaking science news straight to your inbox every day.

Subscribe for FREE

An immune checkpoint blockade antibody blocks the deactivation of the immune system by the cancer cells. The immune system has built-in brakes — called immune checkpoints — so it doesn’t overdo it and injure the body when attacking cancer and infections. Glioblastoma evolves to activate the brakes, and therefore, the immune system (i.e., lymphocytes) won’t attack it.


In addition to the tumor cells, glioblastoma contains other cell populations called macrophages and microglia. These are the most abundant components of the tumor microenvironment and the cells that glioblastoma modulates to inhibit lymphocytes. The study showed that the chemo and antibody cocktail altered these cells, enabling the lymphocytes to recognize and kill the cancer cells.


“This is the first report in humans where an ultrasound device has been used to deliver drugs and antibodies to glioblastoma to change the immune system, so it can recognize and attack the brain cancer,” said co-corresponding author Adam Sonabend, MD, associate professor of Neurological Surgery and a Northwestern Medicine neurosurgeon. “This could be a major advance for the treatment of glioblastoma, which has been a frustratingly difficult cancer to treat, in part due to poor penetration of circulating drugs and antibodies into the brain.”


The study was conducted in four patients who had advanced progression of their tumors. They had already been treated with conventional chemotherapy for their tumors as well as an experimental treatment in a clinical trial, but both times, the tumors returned.


“This is a great example of translational bench-to-bedside-back-to-bench research, which sets an exceptional scenario to learn about the ability of the immune system to kill brain tumors in real-time upon treatment,” said co-corresponding author Catalina Lee-Chang, PhD, assistant professor of Neurological Surgery. “Given the lack of effective immune response against these deadly tumors, these findings encourage us to envision a potential new treatment approach.” 

Clinical trial launched with new treatment

These new findings are the basis for a novel clinical trial that was just launched at Northwestern using ultrasound to deliver immunotherapy for glioblastoma. The trial will initially enroll 10 participants to determine the safety of the treatment, followed by 15 additional to measure whether the treatment can prolong survival.


Previous large clinical trials have failed to show that this type of immunotherapy can prolong survival in glioblastoma patients. Sonabend, however, believes that by enhancing the delivery of these antibodies and drugs into the brain and relying on biomarkers that indicate which tumors are most susceptible to immunotherapy, this treatment might be shown to be effective for some glioblastoma patients.


“Here we show in a small cohort of patients that when you use this technology, you can enhance the delivery of the chemotherapy and the antibodies, and change the tumor’s microenvironment, so the immune system can recognize the tumor,” Sonabend said.


Reference: Arrieta VA, Gould A, Kim KS, et al. Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas. Nat Commun. 2024;15(1):4698. doi: 10.1038/s41467-024-48326-w


This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.