Amplifying STING activation by cyclic dinucleotide-manganese particles for local and systemic cancer metalloimmunotherapy.

ABSTRACT: Nutritional metal ions play critical roles in many important immune processes. Hence, the effective modulation of metal ions may open up new forms of immunotherapy, termed as metalloimmunotherapy. Here, we demonstrate a prototype of cancer metalloimmunotherapy using cyclic dinucleotide (CDN) stimulator of interferon genes (STING) agonists and Mn²⁺. We screened various metal ions and discovered specific metal ions augmented STING agonist activity, wherein Mn²⁺ promoted a 12- to 77-fold potentiation effect across the prevalent human STING haplotypes. Notably, Mn²⁺ coordinated with CDN STING agonists to self-assemble into a nanoparticle (CDN-Mn²⁺ particle, CMP) that effectively delivered STING agonists to immune cells. The CMP, administered either b

SUBMITTER: Sun X 

PROVIDER: S-EPMC8595610 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature