Targeting STING-induced immune evasion with nanoparticulate binary pharmacology improves tumor control in mice.

ABSTRACT: Harnessing the stimulator of IFN genes (STING) signaling pathway to trigger innate immune responses has shown remarkable promise in cancer immunotherapy; however, overwhelming resistance to intratumoral STING monotherapy has been witnessed in clinical trials, and the underlying mechanisms remain to be fully explored. Herein, we show that pharmacological STING activation following the intratumoral injection of a nonnucleotide STING agonist (i.e., MSA-2) resulted in apoptosis of the cytolytic T cells, IFN-mediated overexpression of indoleamine 2,3-dioxygenase 1 (IDO1), and evasion from immune surveillance. We leveraged a noncovalent chemical strategy for developing immunomodulatory binary nanoparticles (iBINP) that include both the STING agonist and an IDO1 inhibitor for treating immune-evas

SUBMITTER: Meng F 

PROVIDER: S-EPMC12700560 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature