Cancer immunotherapy that pairs ultrasound with cancer-killing immune cells to destroy malignant tumors while sparing normal tissue
Bioengineers at the University of California San Diego have developed a cancer immunotherapy that pairs ultrasound with cancer-killing immune cells to destroy malignant tumors while sparing normal tissue. The team, led by the labs of UC San Diego bioengineering professor Peter Yingxiao Wang and bioengineering professor emeritus Shu Chien, detailed their work in a paper published Aug. 12 in Nature Biomedical Engineering.
CAR T-cell therapy has worked well for the treatment of some blood cancers and lymphoma, but not against solid tumors. That’s because many of the target antigens on these tumors are also expressed on normal tissues and organs. This can cause toxic side effects that can kills cells—these effects are known as on-target, off-tumor toxicity. “CAR T cells are so potent that they may also attack normal tissues that are expressing the target antigens at low levels,” said first author Yiqian (Shirley) Wu, a project scientist in Wang’s lab. To combat this issue, the team took standard CAR T cells and re-engineered them so that they only express the CAR protein when ultrasound energy is applied. This allowed the researchers to choose where and when the genes of CAR T cells get switched on. “We use ultrasound to successfully control CAR T cells directly in vivo for cancer immunotherapy,” said Wang, who is a faculty member of the Institute of Engineering in Medicine and the Center for Nano-ImmunoEngineering, both at UC San Diego. What’s exciting about the use of ultrasound, noted Wang, is that it can penetrate tens of centimeters beneath the skin, so this type of therapy has the potential to non-invasively treat tumors that are buried deep inside the body.
The team’s approach involves injecting the re-engineered CAR T cells into tumors in mice and then placing a small ultrasound transducer on an area of the skin that’s on top of the tumor to activate the CAR T cells. The transducer uses what’s called focused ultrasound beams to focus or concentrate short pulses of ultrasound energy at the tumor. This causes the tumor to heat up moderately—in this case, to a temperature of 43 degrees Celsius (109 degrees Fahrenheit)—without affecting the surrounding tissue. The CAR T cells in this study are equipped with a gene that produces the CAR protein only when exposed to heat. As a result, the CAR T cells only switch on where ultrasound is applied. The researchers put their CAR T cells to the test against standard CAR T cells. In mice that were treated with the new CAR T cells, only the tumors that were exposed to ultrasound were attacked, while other tissues in the body were left alone. But in mice that were treated with the standard CAR T cells, all tumors and tissue expressing the target antigen were attacked.
Source: University of California San Diego