A new study from the University of Texas Southwestern Medical Center says it is the first to successfully use nanoparticles to target the STING protein. These nanoparticles, which are only about one millionth the size of a soccer ball, regulate the immune system’s switches and control the immune system’s response to the physiological environment.
STING, an immune protein discovered by scientists only in 2008, stands for stimulator of interferon genes and helps regulate the body’s immune system to fight inflammation and cancer cells.
Over the past decade or so, a large number of researchers and pharmaceutical companies have pinned their hopes on target stimulation of STING proteins to enhance the immune system’s ability to fight tumors and develop natural anti-cancer drugs. However, previous studies have been unsuccessful in clinical trials.
Study leader Jinming Gao, a professor of molecular biology at the University of Texas Southwestern Medical Center, said, “The main limitation of traditional small-molecule drugs is that after being injected into cancer cells, they are quickly washed away in the bloodstream, not only reducing their efficacy but also creating toxicity in the body.”
Professor Gao’s group originally planned to design a polymer, a man-made giant molecule that could self-assemble into nanoparticles, to deliver cyclic guanosine-adenosine monophosphate (cGAMP), a natural small-molecule activator that activates STING proteins, to the STING protein.
They synthesized a polymer called PC7A for this purpose. But in 2017 they discovered that PC7A could still activate the STING protein even in the absence of cGAMP. But they didn’t know exactly why at the Time, nor did they understand why PC7A was different from all other similar drug molecules.
This new study found that PC7A is bound to the STING protein in a different location than other drug molecules, and that it activates the STING protein for up to 48 hours, while other drugs are only effective for about 6 hours. The researchers found that the longer duration of action also allowed the drug to better mobilize T cells in response to multiple solid tumors. When PC7A and cGAMP were combined in mice, tumor growth in mice slowed down and mice survived longer.
Another advantage of PC7A is that it is present in the blood as small spherical nanoparticles and therefore does not bind STING proteins. Only when it enters immune cells does it change to a polymeric form, which binds STING proteins and thus activates the immune response. This advantage is likely to reduce the potential for PC7A to cause side effects elsewhere in the body.
The study also found that because of the specific location of PC7A binding, this complex may help patients who are resistant to other immune-activating drugs. Up to 20% of the population has a slightly different gene for the STING protein, and this subtle difference leads to resistance to multiple cyclic dinucleotide immune drugs. This study demonstrates that PC7A is still effective in these individuals.
The study was published Feb. 8 in the journal Nature Biomedical Engineering.
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