Molecule that activates immune protein STING shows promising results against tumors

Scientists at Scripps Research have discovered a molecule that can activate a natural immune-boosting protein called STING. The findings mark a significant advance in the field of oncology, as the STING protein is known for its strong antitumor properties.

STING (short for Stimulator of INterferon Genes) marches the immune system against viral and cancerous invasions and has received enthusiastic interest from drug developers because of its role in promoting antitumor immunity.

However, the natural activators of STING in the body are unstable DNA-related molecules that do not last long in the bloodstream. This has hindered the development of treatments based on it and prompted a search for a harder STING-activating small molecule – one that can circulate in the blood and work “systemically against tumors” wherever they are in the body can exist.

The scientists from Scripps Research, who reported their findings in Science on August 20 screened a set of suitable small molecules with different structures and identified several that activate STING. After adapting one of these molecules to optimize its properties, they found that systematic delivery in mice with an injection greatly reduced the growth of an aggressive form of melanoma.

The discovery raises the possibility of a circulating drug that could activate STING and suppress a wide range of cancers.

“A systemic STING-activating molecule could have many benefits, not only as a therapeutic for cancer and infectious disease, but also as a probe to study STING-dependent antitumor immunity and a host of other STING-related biological processes,” says co – senior author Luke Lairson, Ph.D., an associate professor in the department of chemistry at Scripps Research.

Lairson and colleagues found that their optimized STING activator, which they named SR-717, appears to activate the STING protein in the same way as its natural activators in the body. Using X-ray crystallography to plot the atomic scale interaction, they showed that both SR-717 and a known natural activator bind to the same site on STING and induce the same shape change in the protein.

In an animal model of aggressive melanoma, SR-717 dramatically suppresses tumor growth, prevents metastasis, induces the presentation of tumor molecules to the immune system, and strengthens tumor levels of CD8 + T cells and NK cells – both known to be single of the most severe antitumor weapons of the immune system. At this effective dose, there was no evidence of significant adverse effects in the animals.

Lairson and colleagues are studying SR-717, hoping to develop it into a new anti-cancer treatment that can only be used in combination with other treatments.