Immune targeting of triple-negative breast cancer through a clinically actionable STING agonist-CAR T cell platform.

ABSTRACT: Stimulator of interferon genes (STING) has emerged as a critical cancer immunotherapy target. However, no STING agonist has advanced beyond phase I/II clinical trials, as obstacles center around applying STING agonism to the appropriate clinical context, retaining it in the tumor microenvironment (TME), and limiting its T cell toxicity. Using triple-negative breast cancer (TNBC), we identify defective STING turnover as a cancer state promoting hypersensitivity to STING agonism. We also repurpose a US Food and Drug Administration (FDA)-approved polyethylene glycol (PEG) biopsy marker to deliver STING agonists in a controlled release fashion into the TME. However, STING agonist-induced T cell toxicity limits robust endogenous clonal T cell response, which can be overcome by sequential co-del

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12281382 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature