In a groundbreaking study published in Cell in April 2025, researchers from the University of Southern California (USC) introduced "EchoBack CAR T-cells," a novel form of chimeric antigen receptor (CAR) T-cell therapy designed to more effectively target solid tumors. These engineered immune cells are activated by a brief, 10-minute pulse of focused ultrasound, enabling them to detect and attack cancer cells in their vicinity.

CAR T-cell therapy has revolutionized the treatment of hematologic malignancies like leukemia by modifying a patient's own T-cells to recognize and attack cancer cells. However, its application to solid tumors has been limited due to challenges such as on-target off-tumor toxicity, T-cell exhaustion, and limited persistence of the engineered cells. The development of EchoBack CAR T-cells addresses these issues by incorporating a feedback mechanism—dubbed "EchoBack" for its call-and-response function—where proximity to tumor cells prompts increased production of cancer-killing molecules. This design minimizes harm to healthy tissue, as the CAR molecules degrade when cells migrate away from tumors.

In laboratory experiments using mouse models, EchoBack CAR T-cells outperformed standard CAR T-cells against prostate cancer and glioblastoma cells. The research team conducted lab-based experiments in mouse models to test the new CAR T-cells on a selection of tumor cells including prostate cancer and glioblastoma. The ultrasound-controllable CAR T-cells, with two rounds of ultrasound stimulation, outperformed standard CAR T-cells. Additionally, when continuously challenged with tumor cells, standard CAR T-cells became exhausted and dysfunctional, whereas the ultrasound-controllable CAR T-cells maintained better function, exhibited less exhaustion, and demonstrated enhanced tumor-killing capabilities.

This advancement offers new hope for patients with difficult-to-treat tumors, potentially reducing the frequency of treatments and improving patient outcomes. The EchoBack CAR T-cells are not just a conceptual innovation but represent a real step toward the future of safe and efficient immunotherapy, offering new hope to patients with difficult-to-treat tumors. The team hopes this new technology could be adapted to other types of solid tumors for immunotherapy, such as breast cancer and retinoblastoma.

Lead author Longwei Liu, an assistant professor at the USC Viterbi School of Engineering, highlighted the practical benefits for patients:

"You can imagine that when patients come to the hospital using the first-generation cells, the patient may need to come in every day for treatment. But using the new generation, the treatment now requires far fewer visits, such as once every two weeks, or even less frequently."

Peter Yingxiao Wang, the Dwight C. and Hildagarde E. Baum Chair in Biomedical Engineering at USC, emphasized the significance of the breakthrough:

"It's definitely a breakthrough. It will make the whole ultrasound-controllable CAR T practically useful for real medical applications."

The development of EchoBack CAR T-cells represents a significant advancement in cancer immunotherapy, particularly for solid tumors. By integrating focused ultrasound as a control mechanism, these engineered cells offer a more precise and sustained approach to targeting cancer cells, potentially transforming treatment protocols and improving patient outcomes.