Remote-Controlled Signal Activates T Cells for Cancer Immunotherapy

Researchers at Georgia Tech have developed a technique to remotely activate genetically-modified T cells to attack cancer. The method employs a near-infrared laser that heats gold nanorods present in the tumor, causing local heating. This heat activates the T cells, making them more aggressive in killing cancer cells.

Immunotherapies, such as T cell therapy, hold significant promise in treating cancer. However, the technique is still very new, and isn’t always effective. “Right now, we’re adept at harvesting a patient’s own T-cells, modifying to target cancer, growing them outside the body until there are hundreds of millions of them,” said Gabe Kwong, a researcher involved in the study. “But as soon as we inject them back into a patient, we lose control over the T-cells’ activity inside the body.”

Some tumors can deactivate T cells, meaning they lose their effectiveness. Numerous research groups are working on improving T cell therapies. The Georgia Tech researchers have developed an on/off switch for T cells, so that they can be activated within the tumor, and then deactivated later, so that they don’t damage healthy tissue elsewhere.

The research team introduced a heat-sensitive genetic “switch” into T cells, which increases the expression of specific proteins when activated by heat, enhancing their cancer-fighting abilities. Using a near-infrared laser from outside the body, the researchers can gently heat gold nanoparticles in the tumor tissues, turning the genetic switch “on”. The effect requires heating of only a few degrees Celsius above body temperature.

However, once the researchers remove the localized heating and the tumor cools down, the T cells return to a non-active state, helping to ensure that they won’t damage healthy tissues elsewhere. “There would be off-target toxicities, so you really want to pinpoint their activation,” said Kwong. “Our long-term goal for them is to activate site-specifically, so T-cells can overcome immunosuppression by the tumor and become better killers there.”

The team tested the approach in tumor-bearing mice, and confirmed that the components of the system worked. “In upcoming experiments, we are implementing this approach to treat aggressive tumors and establish cancer-fighting effectiveness,” said Kwong.

Study in ACS Synthetic Biology: Remote Control of Mammalian Cells with Heat-Triggered Gene Switches and Photothermal Pulse Trains…

Via: Georgia Tech…