CAR T cell therapy is a promising new potential treatment for cancer, but it can trigger dangerous side effects in healthy tissue. Now, researchers at the University of California San Diego have found a way to focus the treatment more precisely, by engineering CAR T cells to only work at elevated temperatures, then heating tumors with ultrasound.
The immune system is our front-line of defense against pathogens and other harmful cells, but cancer can be crafty, using a range of underhanded tactics to evade detection by immune cells. To try to swing things back in our favor, immunotherapy involves removing T cells from a patient, supercharging them to better target cancer antigens, then returning them to the body.
Results have been incredibly promising, particularly against blood cancers, but frustratingly the technique doesn’t seem to work as well on solid tumors. Part of the problem, it seems, is that the invigorated immune cells, known as chimeric antigen receptor (CAR) T cells, can overreact and begin attacking healthy cells that express those antigens at low levels. That can lead to a potentially deadly immune condition known as a cytokine storm.
So for the new study, the researchers added a trigger that would ensure the CAR T cells are only activated at the site of the tumor, minimizing their off-target damage. They engineered the CAR T cells with a gene that only produces the CAR protein when exposed to heat – then, they heated up the tumors to 43 °C (109 °F) using focused pulses of ultrasound.
The team tested the technique by administering the heat-activated CAR T cells to mice with subcutaneous tumors, then using a small ultrasound transducer over the site of the tumor. And sure enough, the treatment suppressed tumor growth while reducing off-target effects, compared to mice that received regular CAR T cell therapy.
“This shows our CAR T-cell therapy is not only effective, but also safer,” says Yiqian Wu, first author of the study. “It has minimal on-target, off-tumor side effects.”
The team plans to perform more tests and investigate toxicity before any human trials can begin.
The research was published in the journal Nature Biomedical Engineering.
Source: UC San Diego