Researchers are looking into a CAR T-cell therapy in which ultrasound waves activate cancer-fighting agents.
In the future, fighting cancer may no longer mean grueling chemotherapy, but genetically altered immune systems that can be “remote controlled.”
That’s currently the hope of researchers based at the University of California, San Diego (UCSD), who are investigating if ultrasound waves can manipulate immune system T cells to effectively create a new form of cancer treatment.
The therapy builds off CAR T-cell therapy, which has revolutionized some cancer treatments.
During CAR T-cell therapy, doctors reengineer patient’s T cells, which are part of the immune system, to identify and fight cancer.
However, the technology has only been approved so far for use in nonsolid tumors.
Experts have been searching for a way to have the immune system target solid tumors without also causing the T cells to attack healthy tissues in key organs, such as the lungs or liver.
In a study published in Proceedings of the National Academy of Sciences last month, Dr. Peter Yingxiao Wang, a bioengineering professor at UCSD and co-author of the study, wanted to find out if using remote-controlled ultrasound could help create a new form of targeted CAR T-cell treatment.
In this early research, Wang and his co-authors focused on making T cells that responded to ultrasound waves in order to activate them.
The team was able to harness a field of research called “mechanobiology.” It focuses on how a cell perceives, senses, and reacts to environmental cues.
The researchers took T cells and added a “mechnosensor” and microbubbles so that the cells would “perceive” the ultrasound waves. They were then genetically engineered to target cancer cells, potentially rendering them “remote-controlled” cancer therapy.
“We repurpose and twist a little bit,” Yang explained in order to understand how they engineered the cell to control its behavior.
“The ultrasound is essentially a sound but with high frequency,” Yang told Healthline. “They basically utilize the mechanical force or mechanical wave to penetrate inside the tissue.”
By utilizing ultrasound waves, Yang could in theory inject a patient with engineered CAR T cells that wouldn’t “activate” unless an ultrasound wave is directed at them.
This could mean a patient with a liver or lung tumor could be treated with the CAR T cells and, in theory, the cells would only start to attack if the ultrasound machine is used in the area where the tumor is present.
This would help protect the patient’s healthy tissue, since the cells would be less likely to mistake important organ tissue for cancer tissue.
This research is still in the early stages and has yet to be proven to work in a cancer patient. But Wang said he hopes it could provide a new pathway for CAR T-cell therapy research that would help more patients.
“This work could ultimately lead to an unprecedented precision and efficiency in CAR T-cell immunotherapy against solid tumors, while minimizing off-tumor toxicities,” Wang said in a statement.
Dr. Rebecca Gardner, an oncologist at Seattle Children’s hospital, said this study is a “pretty nifty idea.”
“What’s really unique about this study is that it’s anatomically specific,” said Gardner, who’s also a principal investigator of two CAR T-cell immunotherapy clinical trials at Seattle Children’s. “You have to have the ultrasound machine that goes to where the CAR T cells are and turns them on only in that location.”
Gardner explained that currently CAR T-cell therapies have been used for blood cancers such as leukemia that are diffuse. However, a solid tumor can pose extra risks for using CAR T-cell therapy.
Gardner said currently ensuring that these therapies don’t target healthy tissue or cause other toxic events in patients is difficult. More research will be needed to keep patients safe.
“We’re going to want to better regulate where CAR T cells are and when they have expression and when they don’t,” Gardner told Healthline.
However, she said this study adds to new research focused on understanding CAR T-cell therapy’s impact on solid tumors, including brain tumors.
“I think brain tumors may be the next thing where CAR T cells can be impactful,” Gardner said. It may be “there’s not a ton of immune system in your brain and it’s a little bit easier to impact it.”
However, she said this field of research will require much more investigation before any of these therapies are being used on a widespread basis.
“There’s so many compelling factors in solid tumors that prevent the immune system from getting there and working,” she said. “It’s not as simple as a solution as, here’s a CAR T cell for a solid tumor.”