New way to help CAR-T cells fight solid tumors could change cancer treatment
For more than a decade, CAR-T cell therapy has been one of the biggest breakthroughs in cancer medicine. By reprogramming a patient's own immune cells to attack cancer, doctors have produced remarkable results against certain blood cancers, offering hope to patients who once had few treatment options.
CAR-T cell therapy has revolutionized treatment of certain blood cancers, but has struggled to effectively target solid tumors such as brain, liver, lung, breast and pancreatic cancers. Researchers at USC Viterbi School of Engineering believe they have developed a new approach called SHIFTERS that could change this.
SHIFTERS temporarily creates a marker on tumor cells by using focused ultrasound to prompt them to display CD19, the same marker that CAR-T cells recognize in blood cancers. By combining this temporary marker with focused ultrasound, which precisely targets tissue deep inside the body, doctors can activate CAR-T cells to attack tumors.
The technique works by exploiting the fact that solid tumors often have low oxygen levels. SHIFTERS recognizes this condition and relies on focused ultrasound to activate the marker for a week. When activated, even a small percentage of cells displaying the marker triggers a broader immune attack on the tumor, making it easier to attack even when tumor cells display the marker.
In preclinical studies using animal models of brain and liver tumors, SHIFTERS enhanced CAR-T cell activity and resulted in dramatic shrinking of tumors compared to untreated tumors. Researchers discovered that only a small percentage of cells displaying the marker was sufficient to launch the attack.
While still experimental, this technology could allow doctors to control when and where CAR-T cells attack tumors by temporarily creating a marker on tumors. The next step is finding a practical way to deliver the SHIFTERS genetic program into tumors, which researchers are currently working on before moving to human trials.
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