Georgia Tech researchers have developed a way to remotely activate the modified T cells from outside the body using a near-infrared laser that very precisely targets cancerous tumors.
Researchers in Gabe Kwong’s engineering immunity lab at Georgia Tech have spent the last decade working to enhance the body’s defense mechanisms against disease and to create better cancer therapies. They recently took that work to the next level by developing a way to remotely activate modified T cells using a near-infrared laser outside of the body that very precisely targets tumors for more effective treatment.
“We are interested in developing new tools to either detect T cells or engineer T cells for therapies,” says Kwong, an assistant professor at Georgia Tech’s Wallace H. Coulter Department of Biomedical Engineering.
The research is happening as bioengineers continue to make strides in developing T cell-based immunotherapies. The process fights cancers by enhancing the body’s defense system by removing T cells, genetically modifying them, and returning them to the patient’s body. Georgia Tech also spearheaded a new consortium among academia, industry, and governments to increase the production and expand the use of cell therapies.
Despite those advances, there’s still a lot of work that needs to be done.
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T cells are a type of white blood cell that play a major search-and-destroy role in the body’s immune system. Sometimes, though, T cells don’t recognize cancerous tumors as enemies that should be attacked. In other instances, tumors can shut down the T cells’ cancer-killing abilities. Another challenge is how to control T cells after they are returned to the body and make sure they specifically target diseased cells and not healthy ones.
While researchers are adept at harvesting T cells and reinserting them into a patient, they haven’t been able to control them once they’re back in the body, Kwong says. His new process involves embedding T cells with gold nanorods that act as a genetic switch that can be turned on by a laser.
In tests on mice, a laser is pulsed outside of the mouse’s body, right above where the tumor is located. The gold nanorods heat up, causing local heating. That energy flips the engineered T cells switch “on,” making the cells more aggressive.
Kwong likens the approach to a television remote that sends out a near-infrared light to the receiver.
“We are doing almost the same thing. We are using a laser light which has a near-infrared window so you can’t see it. Depending on where you point it or focus it, that area gets heated,” he says. “So we can have very spatially controlled delivery of these T cells.”
This technique, Kwong says, is an improvement over how immunotherapy has been delivered in the past, which is not targeted but generally delivered throughout the entire body. Kwong believes his technique will work for many different types of cancer. “The general framework of being able to remotely control the T cells, that’s the platform idea and that will bridge to all types of cancer,” Kwong says. “It will be agnostic as to what the type of tumor will be.”
The biggest challenges that remain are adapting the technique and targeting it to specific types of cancer cells and different types of cancer subsets. Lung cancer, for example, would require a different way of targeting than brain cancer or prostate cancer. “For some tumors, we are very good. We’ve learned a lot in the last 10 years about how to treat tumors with T cells; for example, melanoma,” Kwong says. “For other type of cancers that might take a little longer.”
One reason there has been success with melanoma is that those cancers accumulate a lot of mutations from exposure to the sun.
“T cells in the body in the body have been trained not to attack cells that look exactly like our own body cells, so when a cancer cell arises and it’s mutated there are flags that say that’s different from a healthy cell,” Kwong says. “The more mutations there are, it’s easier for the body to say ‘Oh that doesn’t look like a healthy cell,’ and it will attack it.”
Overcoming those challenges is probably the final step before the technology moves into either the licensing or a startup phase, which will probably happen between one and three years, he says. “We are always thinking deeply about how to get the tools we are developing into the clinic,” Kwong says.
Nancy S. Giges is an independent technical writer based in White Plains, NY.
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