A groundbreaking approach to treating aggressive brain cancers has emerged from research conducted by teams at Washington University School of Medicine in St. Louis and Northwestern University in Illinois. This innovative method uses nasal drops to deliver tumour-fighting medicine directly to the brain, showing promising results in eliminating glioblastoma tumours in mice.
Glioblastoma, recognized as the most prevalent type of brain cancer, poses significant treatment challenges. These tumours are often classified as “cold tumours” because they fail to trigger the body’s natural immune response, unlike “hot tumours,” which respond more readily to immunotherapy. Researchers have made strides in stimulating an immune reaction against glioblastoma by activating a cellular pathway known as STING (stimulator of interferon genes). STING is activated when cells detect foreign DNA, prompting the immune system to respond.
Previous studies indicated that activating STING in glioblastoma could enhance the body’s immune response against the cancer. However, the drugs used in these treatments tend to break down quickly, requiring direct delivery into the tumour through invasive procedures. To address this limitation, the research teams developed a method to use a new class of spherical nucleic acids to activate the STING pathway in targeted immune cells via nasal delivery.
The study revealed that when the treatment was administered through nasal drops, the medicine traversed the main nerve pathway connecting facial muscles to the brain. This delivery method successfully triggered an immune response concentrated in specific immune cells, particularly in the tumour itself, and also elicited beneficial responses in nearby lymph nodes. Notably, the treatment did not disseminate to other body parts, minimizing the risk of side effects.
Examinations of immune cells in and around the tumour confirmed that the therapy effectively activated the STING pathway, empowering the immune system to combat the cancer. When combined with drugs designed to stimulate T lymphocytes, another type of immune cell, the new therapy achieved tumour eradication with just one or two doses. This combination also induced long-term immunity against potential recurrence, outperforming existing STING-activating therapies.
Speaking on the significance of this research, Alexander H. Stegh, PhD, a professor and co-corresponding author of the study, stated, “We wanted to change this reality and develop a non-invasive treatment that activates the immune response to attack glioblastoma.” He emphasized that the research demonstrates how precisely engineered nanostructures, such as spherical nucleic acids, can safely and effectively activate critical immune pathways in the brain.
Dr. Stegh noted that merely activating the STING pathway may not be sufficient to overcome glioblastoma, as these tumours possess mechanisms to inhibit the immune response. His team is actively exploring additional capabilities for their nanostructures to enhance immune responses further, potentially allowing for a broader therapeutic target within a single treatment.
The findings represent a significant advancement towards safer and more effective treatments for glioblastoma and other cancers that resist immune therapies. Dr. Stegh expressed optimism, saying, “This approach offers hope for safer, more effective treatments for glioblastoma and potentially other immune treatment-resistant cancers, marking a critical step toward clinical application.”
As the research continues, the scientific community eagerly anticipates further developments that could change the landscape of cancer treatment.
