Researchers at the USC Viterbi School of Engineering believe they have found a new approach on CAR-T cells that offers hope of success against solid tumors. Their solution is called SHIFTERS. Instead of searching for a naturally occurring marker that may not even exist, the researchers developed a way to temporarily create one. Using focused ultrasound, physicians prompt tumor cells to briefly display CD19, a marker CAR-T cells already recognize. The work is described in the study,“Ultrasound Priming Gated by Solid Tumor Hallmarks to Guide CAR-T Therapy” in Science Advances. The idea behind SHIFTERS is surprisingly straightforward. Most solid tumors have characteristics that healthy tissue does not. One of those characteristics is low oxygen. As tumors grow rapidly, they often outgrow their blood supply, leaving pockets of cancer cells starved for oxygen.The USC researchers designed SHIFTERS to recognize that condition. But low oxygen alone isn’t precise enough to activate the system. Doctors must also apply focused ultrasound, a noninvasive technology that can precisely target tissue deep inside the body without surgery. The researchers first tested SHIFTERS in cancer cells grown in the laboratory. Next came three-dimensional tumor models that more closely resemble real tumors. Finally, they tested the technology in animal models carrying human brain and liver tumors. Across every stage, the results pointed in the same direction. Once ultrasound activated the temporary marker, CAR-T cells mounted a much stronger attack than they normally achieve against solid tumors. Tumors treated with ultrasound shrank dramatically, while untreated tumors continued to grow.