Taking on an Evasive Threat

Credit: Rita Elena Serda, Baylor College of Medicine, National Cancer Institute 

With certain cancers, including melanoma and some brain cancers, up to half of the time an important stretch of DNA called 9p21 gets deleted. With its disappearance, cancer cells avoid detection by the body’s immune system. Now UT Austin researchers, led by Everett Stone, research associate professor in the Department of Molecular Biosciences, are working with a drug that appears to restore immune cells’ ability to detect and fight these cancers.

In many cases, cancer deletion of genetic code causes a chain of events that both inhibits the regular functioning of immune cells and make it more difficult for immunotherapy treatments to work. In animal models, however, the new drug from the UT Austin team has been found to restore the immune system’s ability to fight, while advancing effectiveness of immunotherapy treatments given at the same time. 

“We see a lot more T cells around the tumor, and they’re in attack mode,” said Stone. “T cells are an important immune cell type, like a SWAT team that can recognize tumor cells and pump them full of enzymes that chew up the tumor from the inside out.”

Stone and team’s drug uses an engineered version of a naturally occurring enzyme. The enzyme breaks down a key compound that the cancers produce, which restrains the body’s ability to fight disease. Genetic modifications and formulation of the enzyme help give the drug staying power. 

“If we injected just the natural enzyme, it would be eliminated within a few hours,” said Stone. “In mice, our modified version stays in circulation for days. In humans, it will last even longer.”