Major Cancer Breakthrough Could Help More Patients Than Previously Thought

A groundbreaking technique developed by researchers at the USC Viterbi School of Engineering could revolutionize cancer treatment for solid tumors, a type of cancer that has historically been difficult to target with CAR-T cell therapy. CAR-T cell therapy, which involves adding a lab-made gene to a patient's T cells to help them detect and kill cancerous cells, has been a major breakthrough in cancer treatment for blood cancers over the past decade.

However, its effectiveness against solid tumors has been limited due to their complex structure and lack of a clear target for CAR-T cells.

The new approach, called SHIFTERS, addresses this challenge by using focused ultrasound to temporarily mark hard-to-target tumors with a marker that CAR-T cells can recognize. This marker is only displayed by the tumor cells that meet two conditions: low oxygen levels and the presence of focused ultrasound. Once both signals are met, the CAR-T cells are directed precisely to the tumor cells, allowing for a more specialized and effective attack.

The researchers, including doctoral student Tianze Guo and researcher Peter Yingxiao Wang, tested the approach in laboratory-grown cancer cells, tumor models resembling real tumors, and animals. They found that CAR-T cells launched a much stronger attack against solid tumors when using the ultrasound method, resulting in significant tumor shrinkage.

Importantly, just 10 to 25 percent of tumor cells needed to display the temporary marker to initiate the immune attack, as this was enough to destroy neighboring cancer cells throughout the tumor.

While the research is still in the experimental stage and has yet to be tested on humans, the researchers are optimistic about the potential of SHIFTERS. However, they acknowledge that there are still hurdles to overcome, particularly in finding a practical way to deliver the SHIFTERS genetic program directly into tumors. The team is exploring two delivery methods, lipid nanoparticles and modified viruses, before moving on to larger animal studies and eventual human trials.