Improving CAR T Cell Therapy with Heat

A team of researchers led by bioengineers at the Georgia Institute of Technology is expanding the precision and ability of CAR T cell therapy. They’ve added a genetic on-off switch to the cells and developed a remote-control system that sends the modified T-cells on a precision invasion of the tumor microenvironment, where they kill the tumor and prevent a relapse. Their work was recently published in Nature Biomedical Engineering.

The latest study builds on the lab’s body of work exploring remotely controlled cell therapies, in which the researchers can precisely target tumors, wherever they are in the body, with a local deposition of heat. “And this heat basically activates the CAR T-cells inside the tumors, overcoming the problems of immunosuppression,” said lead researcher Gabe Kwong.

To generate heat in a mouse’s tumor, they shone laser pulses from outside the animal’s body, onto the spot where a tumor is located. Gold nanorods delivered to the tumor turn the light waves into localized, mild heat, raising the temperature to 40-42 Celsius (104-107.6 F), just enough to activate the T-Cells’ on-switch, but not so hot that it would damage healthy tissue or the T-cells. Once turned on, the cells go to work, increasing the expression of cancer-fighting proteins. The novelty Kwong said, was in genetically engineering clinical-grade CAR T-Cells, something the team worked on for the past three years. Now, in addition to a switch that responds to heat, the researchers have added a few upgrades to the T-cells, rewiring them to produce molecules to stimulate the immune system.

“These cancer-fighting proteins are really good at stimulating CAR T-cells, but they are too toxic to be used outside of tumors,” said Kwong. “They are too toxic to be delivered systemically. But with our approach, we can localize these proteins safely. We get all the benefits without the drawbacks.”