Chimeric antigen receptor (CAR) T-cell therapy has emerged as a highly promising cancer treatment, especially for bloodborne cancers like leukemia. This highly personalized therapy involves extracting T-cells from a patient’s blood, modifying them genetically to improve their ability to identify and destroy cancer cells. Researchers have now taken a significant step forward by developing a new form of CAR T-cell therapy called the “EchoBack CAR T-cell,” a technology that could revolutionize cancer immunotherapy by targeting stubborn solid tumors. This innovation, detailed in the scientific journal Cell, offers a new approach to overcoming key challenges in treating tumors that are typically resistant to immunotherapy while protecting healthy tissue.

Biomedical engineers from the Viterbi School of Engineering at the University of Southern California (Los Angeles, CA, USA) have demonstrated that the EchoBack-CAR T-cells can remain active in attacking tumor cells for five times longer than traditional CAR T-cells, making them highly effective for extended periods. The technology is ready for medical applications and can be controlled remotely to target tumors with focused ultrasound, enhancing both the safety and efficacy of treatments. In comparison to first-generation ultrasound-controllable CAR T-cells, which typically attack cancer cells for only up to 24 hours before depleting, the EchoBack-CAR T-cells can target and destroy cancer cells for at least five days without tiring. The team’s focused ultrasound technology acts as an “on switch” for the CAR T-cells, triggering them with a brief, 10-minute pulse of ultrasound, which activates the cells to detect and target cancer cells nearby.

The name “EchoBack-CAR” stems from the cells' unique mechanisms that mimic the ultrasound stimulation used to activate them. These cells have a feedback system, referred to as the “back” in EchoBack, which allows them to respond to tumor cells and activate themselves to initiate the attack. In laboratory experiments using mouse models, the team tested these enhanced CAR T-cells against various tumor types, including prostate cancer and glioblastoma. The results were compelling, with the ultrasound-controlled CAR T-cells outperforming the standard CAR T-cells, even after being repeatedly exposed to tumor cells. While the traditional CAR T-cells became exhausted and dysfunctional, the new EchoBack-CAR T-cells continued to function optimally, killing cancer cells more effectively.

This breakthrough offers new potential for more powerful, precise, and patient-friendly cancer treatments. The research team believes that the EchoBack CAR T-cells are not just a theoretical concept but a tangible step toward safer and more efficient immunotherapy, giving hope to patients with hard-to-treat tumors. The team is optimistic that this new technology can be adapted as a modular tool for targeting other solid tumors, such as breast cancer and retinoblastoma, expanding the possibilities of immunotherapy for a broader range of cancer patients.

“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,” said lead author Longwei Liu, an assistant professor at the USC Viterbi School of Engineering.

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