A team of bioengineers from the Georgia Institute of Technology is expanding the precision and power of the therapy that is already revolutionizing oncology.
CAR-T cell therapy has been hailed by patients, clinical researchers, investors and the media as an exceptional cure for certain types of cancer.
What CAR-T therapy consists of
Therapy involves engineering a patient's T cells, a type of white blood cell, in the laboratory. A chimeric antigen receptor (CAR) is then added, and finally the "personalized" CAR-T immune cells are returned to the patient's body, where they search for and destroy cancer cells. That's how it works, when it works.
It is a new, evolving and booming area of immunotherapy. There are now over 500 clinical trials worldwide investigating CAR-T cells for the treatment of cancer.
CAR-T: for many, but not for everyone
CAR-T therapy has been shown to be very effective for patients with liquid cancers that circulate in the blood, such as leukemia
Gabe Kwong, Department of Biomedical Engineering at Georgia Tech and Emory.
Unfortunately, for solid tumors (sarcomas, carcinomas) CAR-T's don't work well, for several reasons. A big problem is that CAR-T cells are immunosuppressed by the tumor microenvironment.
Kwong and colleagues are making some cellular changes to improve the way CAR-T cells fight cancer. They added an "on-off genetic switch" to the cells, and developed a remote control system that sends the modified T cells on "precision missions" to the tumor microenvironment, where they kill the tumor and prevent recurrence.
The team illustrated the new method in a study recently published in the journal Nature Biomedical Engineering.
The latest study
Kwong and colleagues explore the possibility of remotely controlling cell therapies. A way to "aim" with precision at the tumorswherever they are in the body. Like? activating CAR-T cells with heat when they are already inside the tumors, overcoming the problems of immunosuppression.
In a mouse test, the researchers irradiated laser pulses from outside the animal's body to where the tumor is. Gold nanotubes injected into the tumor area transformed the light waves into localized heat, raising the temperature to 40-42 degrees Celsius (104-107,6 F). That's enough to activate the CAR-T cell switch, but not so hot that it would damage HEALTHY tissues, or the CAR-T cells themselves.
Once "turned on," CAR-T cells begin to do their job by increasing the expression of cancer-fighting proteins.
An incredible genetic upgrade
The real novelty of this study, says Kwong, is genetic engineering applied to CAR-T cells. Hard work, which took him the last three years.
CAR-T cells now have a "switch" that responds to heat and other upgrades: they have literally been "rewired" to produce molecules that stimulate the immune system. And to produce them only where they are needed.
These cancer-fighting proteins are really effective, but they are too toxic to be administered systemically. With our approach we get all the advantages without the disadvantages.
Gabe Kwong
The results? Extraordinary
The latest study shows that CAR-T therapy cured cancer in mice. The team's approach not only killed the tumors, it also prevented relapses, which is critical for long-term survival.
Further studies will further delve into the personalization of CAR-T cells and how heat will be radiated to the tumor area.
"On humans we will use focused ultrasound, which is absolutely non-invasive and capable of targeting any site in the body," says Kwong. "One of the limitations of the laser is that it doesn't penetrate very far into the body. In the case of deep malignancy, this is a problem. We want to eliminate the problems."
