Researchers have turned to drug delivery nanoparticles to maximize the anti-cancer STING of a molecule, pointing to a possible way to unlock the potential of a pathway that has caught the eye of the industry.
The discovery that mice that lack the stimulator of interferon gene (STING) protein pathway are unable to mount effective anti-cancer immune responses spurred interest in the target and led drug developers including GSK to write checks. However, the natural ligands for STING have properties that necessitate intratumoral delivery. Other systemic candidates suffer poor tumor-targeting and toxicity.
Researchers at the University of Chicago identified nanoparticles as a possible solution. By encapsulating bacterial-derived cyclic dimeric adenosine monophosphate (CDA) in nanoscale coordination polymers (NCPs), the researchers created the tumor-targeted STING agonist ZnCDA.
“This has tremendous potential because we’re not limited to a single compound. We can formulate other nucleotides and use other drugs in the same NCP. The technology is versatile, and we are exploring ways to optimize formulations to take more NCP candidates into clinical trials,” Wenbin Lin, Ph,D., the James Franck Professor of Chemistry at UChicago, said in a statement.
To test the candidate, Lin and his collaborators, who published their findings in Nature Nanotechnology, assessed the effects of single doses in a range of preclinical cancer models. The studies suggest ZnCDA reinvigorates the anti-tumor activity of radiotherapy and checkpoint inhibitors in immunologically "cold" pancreatic and glioma tumor models.
Based on the study, ZnCDA appears to preferentially target tumor-associated macrophages to modulate antigen processing. If the researchers are right, the candidate will promote both innate and adaptive immunity to enhance the efficacy of other molecules.