Researchers at Wake Forest University School of Medicine have developed a new strategy to combat brain metastases, a frequent and often fatal complication of lung cancer. The approach utilizes engineered immune cells, specifically CAR macrophages (CARMAs), designed to target and destroy cancer cells that have spread to the brain, according to a study published online today in Nature Biomedical Engineering.
Brain metastases occur in nearly one in three patients diagnosed with lung cancer, presenting a significant challenge for treatment. Current options, including surgery and radiation therapy, are often limited by the blood-brain barrier, a protective mechanism that prevents many drugs from reaching the brain. The research team, led by Shih‑Ying Wu, Ph.D., assistant professor of radiation oncology at Wake Forest University School of Medicine, sought to overcome this obstacle by leveraging the natural ability of macrophages to cross into the brain.
“Brain metastases are incredibly difficult to treat since most therapies simply can’t gain inside the brain,” Wu said. “Macrophages, however, naturally know how to cross into the brain. So, we asked: ‘What if we could give them the ability to recognize and destroy cancer cells once they get there?’”
The team engineered macrophages to express a chimeric antigen receptor (CAR) that specifically targets mesothelin, a protein found in high concentrations on lung cancer cells that have metastasized to the brain. To further enhance the macrophages’ effectiveness, they incorporated a signaling component called MyD88, which strengthens the cell’s immune response. These MyD88‑CAR macrophages were then tested in laboratory and mouse models designed to replicate lung cancer brain metastasis.
The engineered macrophages demonstrated an ability to enter the brain, locate cancer cells, and slow tumor growth in preclinical models. This research builds on the growing field of immunotherapy, which aims to harness the power of the body’s own immune system to fight cancer. Atrium Health Wake Forest Baptist Comprehensive Cancer Center, the partner institution to Wake Forest University School of Medicine, is actively involved in advancing cancer care through clinical trials, with more than 1,000 trials nationwide.
Atrium Health Wake Forest Baptist has too been a pioneer in CAR T-cell therapy, another form of immunotherapy, offering it on an outpatient basis – the first facility in the Triad region to do so. CAR T-cell therapy reprograms a patient’s T-cells to recognize and attack blood cancers, providing a “smarter playbook” for the immune system, according to Atrium Health.
The study’s findings represent a promising step toward developing new treatments for brain metastases, but further research is needed to determine the safety and efficacy of CARMA therapy in humans. The next steps involve refining the engineered cells and conducting clinical trials to assess their potential in patients.
