A Ribonucleoprotein Approach to Boost the STING Signaling for Cancer Immunotherapy

Technology 

The technology operates by first fusing a tumor epitope to the cytosolic domain of the recombinant transmembrane domain-deficient STINGΔTM protein. Next, the peptide-STINGΔTM protein is mixed with the STING agonist cGAMP, which causes the complex to self-assemble into stable tetramers. These cGAMP-STINGΔTM tetramers improve trafficking of the peptide to lymph nodes, where immune activation can occur. Once delivered, the cGAMP/STINGΔTM complex acts both as a protein carrier for the peptide and as an adjuvant by triggering downstream STING signaling. This allows the vaccine to stimulate immune responses even when endogenous STING expression is silenced.     

Problem Addressed 

Current STING agonist therapies utilize cyclic dinucleotides (CDNs) such as cGAMP. CDNs are difficult to deliver to the cytoplasm where STING is located due to their hydrophilic, negatively charged nature, and their rapid clearance in vivo. Furthermore, many tumors exhibit reduced or absent STING expression through epigenetic silencing, and approximately 19% of the population carries STING variants that respond poorly to natural CDNs. This technology overcomes these barriers by delivering a preassembled STINGΔTM-GAMP complex that activates STING signaling independently of endogenous STING.  

Advantages 

• Enhances STING agonist delivery and activation using a preassembled CDN-STING ribonucleoprotein (RNP) complex, improving therapeutic efficacy.  

• Activates STING signaling in STING-deficient or epigenetically silenced tumors, enabling treatment of cancers that may not respond to conventional STING agonists. 

• Integrates with existing immunotherapy approaches, including immune checkpoint inhibitors and personalized neoantigen vaccines, for combination treatment strategies.