In a significant breakthrough for the treatment of the aggressive brain cancer glioblastoma, researchers successfully utilized ultrasound technology to breach the blood-brain barrier and administer a low dose of a combination of chemotherapy and immunotherapy drugs. The research showed that this method enhanced the immune system’s ability to identify the cancer cells, potentially paving the way for a new treatment approach.
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 revealed that the treatment increased the immune system’s ability to recognize cancer cells, potentially opening up new avenues for treatment.
A group of researchers has made significant progress in a recent study set to be released in Nature Communications on Thursday, June 6.
The researchers demonstrated, for the first time, that an ultrasound device implantable in the skull can improve the delivery of the chemotherapy drug doxorubicin and immune checkpoint blockade antibodies—a new combination treatment for immunotherapy—into the human brain. This device creates microbubbles that temporarily open the blood-brain barrier, allowing for enhanced penetration.The scientists have discovered a way to break through the blood-brain barrier, allowing immunotherapy to reach the brain. Additionally, they have found that a low dose of doxorubicin, when combined with immune checkpoint antibodies, can enhance the immune system’s recognition of malignant glioblastoma cells and rejuvenate the lymphocytes responsible for attacking the cancer cells. This antibody works by blocking the deactivation of the immune system by cancer cells, which have built-in brakes to prevent overactivity and injury.The immune system plays a crucial role in fighting cancer and infections. Glioblastoma, a type of brain cancer, has the ability to deactivate the immune system’s ability to attack it by activating certain mechanisms. In addition to the cancer cells, glioblastoma contains other cell populations known as macrophages and microglia, which are the most abundant components of the tumor microenvironment. The cancer cells manipulate these cells to prevent the immune system from attacking. However, a recent study found that a combination of chemotherapy and antibodies was able to change these cells, allowing the immune system to recognize and destroy the cancer cells. This is an important development in the field of cancer treatment, as it is the first time that an ultrasound device has been used to deliver such treatment in humans.The use of drugs and antibodies in treating glioblastoma aims to modify the immune system’s response to the brain cancer, according to co-corresponding author Dr. Adam Sonabend, who is an associate professor of neurological surgery at Northwestern University Feinberg School of Medicine and a neurosurgeon at Northwestern Medicine. He believes that this approach could represent a significant breakthrough in the treatment of glioblastoma, a notoriously challenging cancer to treat, largely due to the limited ability of drugs and antibodies to reach the brain.
The research involved four patients with advanced tumor progression who had previously undergone treatment with conventionalConventional chemotherapy was administered to patients to treat their tumors, along with an experimental treatment in a clinical trial. However, in both cases, the tumors came back. Co-corresponding author Catalina Lee-Chang, assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine, referred to this as a prime example of translational research. This research provides valuable insight into the immune system’s ability to combat brain tumors in real-time during treatment. The findings are particularly encouraging as there is currently a lack of effective immune response against these types of tumors.
“We envision a potential new treatment approach.”
Clinical trial launched with new treatment
These recent discoveries have led to the initiation of an innovative clinical trial at Northwestern, in which ultrasound will be used to administer immunotherapy for glioblastoma. The trial will begin with 10 participants to assess the safety of the treatment, followed by an additional 15 to evaluate its potential to extend survival.
Prior large-scale clinical trials have not proven the ability of this type of immunotherapy to prolong survival in glioblastoma patients. However, Sonabend is optimistic that by improving the delivery, The use of these antibodies and drugs in the brain, along with the use of biomarkers to identify which tumors are most responsive to immunotherapy, may prove to be effective for some glioblastoma patients.
“Our research with a small group of patients demonstrates that utilizing this technology can improve the delivery of chemotherapy and antibodies, and also alter the tumor’s microenvironment to enable the immune system to recognize the tumor,” explained Sonabend.
Sonabend and Lee-Chang are affiliated with the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Malnati Brain Tumor Institute. Sonabend is also rnrnFeinberg’s director of translational neuro-oncology is the lead author of the article titled “Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas.” The article also includes contributions from other Northwestern authors such as Vi?ctor A. Arrieta, Andrew Gould, Kwang-Soo Kim, Karl J. Habashy, and many others.
The study was funded in part by the National Cancer Institute, National Institutes of Health, and other organizations including the Moceri Family Foundation and the Panattoni family.
