Scientists have developed new nanoparticles that have the potential of augmenting the body’s immune response and fight against cancer through intravenous cancer immunotherapy.
As it goes, cancer immunotherapy seeks to turn “cold” tumors into “hot” tumors––those that respond to immunotherapy––by awakening and enlisting the body’s own immune system. However, there are immune checkpoint inhibitors that make the treatment methodology not successful in many people.
Scientists have long been looking to find new and safe molecules that could augment body’s immune response and latest clinical trials have shown that the STING agonist could be the one. STING is a protein essential to the immune response against infection as well as cancer.
In searching for molecules that would augment the STING pathway, a team of scientists at the University of Michigan School of Pharmacy and the Rogel Cancer Center looked to nutritional metal ions, which we absorb from food, and are important for immune regulation.
They found that adding the nutritional metal ion manganese to STING agonists boosted STING’s tumor-fighting capability up to 77-fold, compared to STING agonists used alone, said James Moon, the J.G. Searle Professor of Pharmaceutical Sciences and professor of biomedical engineering.
When researchers added the manganese ions to STING agonists, they formed nano-sized crystals, which significantly increased cellular uptake of STING agonists and STING activation by immune cells. To develop a STING agonist for intravenous administration, the researchers coated these nanocrystals with a lipid layer (similar to those found in mRNA COVID19 vaccines), resulting in a nanoparticle system called CMP.
Most STING agonists must be delivered directly into the tumor, but this isn’t suitable for metastatic cancers, a major cause of mortality. Even with intratumoral injections, conventional STING agonists are challenged by limited clinical response.
It is the first time that nanoparticles delivering STING agonists and metal ions have been developed for intravenous cancer immunotherapy, and this could open new doors for cancer immunotherapy treatments.
The team demonstrated the tumor-fighting effects of CMP in various tumors, including colon carcinoma, melanoma, and head and neck cancer.
The study team is currently working to test the safety and efficacy of CMP in large animals.