CAR-T cell therapy holds tremendous potential for treating cancer, but researchers have been challenged by the lack of markers the engineered immune cells can recognize in mesothelioma and other solid cancers. But in a study published in the journal Science Advances, scientists at the USC Viterbi School of Engineering report having developed a revolutionary system called SHIFTERS that uses focused ultrasound to temporarily create targets on these tumors. This innovation potentially solves one of CAR-T cell immunotherapy’s biggest obstacles.
Mesothelioma and Solid Tumors Lack the Surface Markers CAR-T Cells Target
Mesothelioma is characterized by solid tumors, which are abnormal masses of tissue that generally do not contain cysts or liquid areas. They are distinct from blood cancers like leukemia, which generally do not form masses. CAR-T cell therapy has been effective against blood cancers because it engineers a patient’s own immune cells to recognize and attack cancer cells displaying specific surface markers. Because mesothelioma and other solid tumors don’t express these antigens on their cell surface, CAR T cells don’t easily recognize them.
To address this challenge for patients with mesothelioma and other solid tumors, the researchers developed what they call the SHIFTERS system, which creates a temporary target for immunotherapy. The group made use of the low oxygen levels that are characteristic of solid tumors outpacing their blood supply, using the condition as an activation key in combination with focused ultrasound that precisely targets tissue deep inside the body. They found that when both low oxygen and focused ultrasound are present, the solid tumor cells briefly display CD19, a marker that CAR-T cells recognize.
Ultrasound Approach Leverages Mesothelioma’s Low Oxygen Levels
According to the researchers, aiming the focused ultrasound on the low-oxygen tumor cells triggers cancer cells to briefly display a visible target for the engineered immunotherapy cells. The marker remains for approximately one week, allowing physicians to control precisely where and when the immune attack begins. “The goal is to make solid tumors easier to recognize while giving doctors control over where and when treatment switches on,” said researcher Tianze Guo.
In laboratory models and animal studies, mesothelioma and other solid tumors exposed to the ultrasound-guided system shrank substantially while untreated tumors continued growing. Notably, not every cancer cell needed to display the marker for the treatment to produce a broader tumor-attacking response. The technology is still experimental, and it will likely be years before it can be tested on humans, but it demonstrates a genuinely new method for bringing CAR-T therapy to mesothelioma and other solid tumors that have resisted it.
If you or someone you love has been diagnosed with mesothelioma, the Patient Advocates at Mesothelioma.net are here to help. Contact us today at 1-800-692-8608 to learn more.
