Focused ultrasound gives CAR-T cells a temporary target in solid tumors

A tumor does not need to wear the new signal on every cell. In experiments led by researchers at the USC Viterbi School of Engineering, focused ultrasound helped a small share of solid-tumor cells temporarily display CD19, a marker already recognized by engineered CAR-T immune cells. Those cells then helped direct an attack across the wider tumor.

The system, called SHIFTERS, uses a two-part trigger. One signal is low oxygen, a condition common inside rapidly growing solid tumors. The second is focused ultrasound, which can target tissue deep inside the body without surgery. Only when both conditions are present do tumor cells briefly produce CD19, and the marker remains for about a week.

That gives the approach a different starting point from the usual search for a natural antigen—a surface marker that appears on cancer but not healthy tissue. Solid tumors arise from normal tissues and often share many of their features, making such a perfect target difficult to find. SHIFTERS instead tries to create a temporary target where physicians want CAR-T cells to act.

The researchers moved from laboratory-grown cancer cells to three-dimensional tumor models and then to animals carrying human brain and liver tumors. In each setting, ultrasound activated the marker and produced a much stronger CAR-T attack than normally seen against solid tumors. The team reports that 10% to 25% of cells carrying the initiating target were enough to drive substantial killing across the tumor, including unmarked cells.

So what changes in practice? Not treatment today: SHIFTERS has not yet been tested in people, and the biggest unresolved problem is how to deliver its genetic program directly into tumors. The team is comparing lipid nanoparticles with modified viruses before larger animal studies and eventual human trials. For patients with solid tumors, the potential shift is more basic but significant: instead of waiting for cancer to reveal a usable target, doctors might one day switch one on temporarily and locally.