Engineered Sonogenetic CAR T Cells Show Extended Cancer-Fighting Capability

A team of biomedical engineers from the University of Southern California (USC) has developed a novel type of engineered immune cell called the EchoBack CAR T cell, designed to target solid tumors more effectively than existing therapies. Published in Cell, the research demonstrates that these cells can attack cancer cells for up to five days following a brief ultrasound activation, a significant improvement over first-generation ultrasound-controllable CAR T cells, which typically function for less than 24 hours. 

Chimeric antigen receptor (CAR) T-cell therapy, which modifies a patient’s own immune cells to target cancer, has shown success against blood cancers like leukemia but struggles with solid tumors. The USC team, led by Peter Yingxiao Wang and Longwei Liu, engineered EchoBack CAR T cells to respond to a 10-minute ultrasound pulse, triggering activation within tumors. Once stimulated, the cells sustain their cancer-killing activity without exhausting quickly, even when repeatedly exposed to tumor cells.

The patient may need to come in every day for treatment with first-generation cells. With EchoBack, visits could be reduced to once every two weeks or less, Liu explained. The cells also incorporate 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 lab experiments using mouse models, EchoBack CAR T cells outperformed standard CAR T cells against prostate cancer and glioblastoma cells. “We can clearly see that the ultrasound controllable CAR plus two rounds of ultrasound stimulation outperformed the standard CAR T cells,” Liu said. “Also, when we kept challenging our CAR T cells with tumor cells, the standard CAR was already exhausted and in a dysfunctional state, but our ultrasound controllable CAR has a better function, less exhaustion and more enhanced killing.”

According to the team, this approach offers new hope to patients with difficult-to-treat tumors. “The most exciting part is that the CAR T cells are smart. They can listen to the ultrasound and sense the tumor cells. These types of CAR T cells have never been developed previously, and we are looking forward to its benefits for patients in the future.”