Engineered T cell-agonist chimera for logic-gated STING activation and augmented cancer immunotherapy.

A TAM-targeted, logic-gated STING-activating T cell–agonist chimera (SNTC) achieves over 40% survival beyond 60 d in melanoma tumor–bearing mice.

• Why it matters: Solid tumors suppress adoptive T cell activity, and STING activation in the tumor microenvironment is needed to improve infiltration and cytotoxicity.
• What they did: The authors engineered SNTC with covalent surface anchoring so a nanoagonist is locally released in tumors via T cell surface reduction potential and restored in TAM by glutathione, enabling AND-gated STING activation.
• The result: SNTC reshapes tumor stroma and boosts TAM antigen presentation to support adoptive T cells, and in orthotopic pancreatic tumor mice, SNTC with immune checkpoint blockade yields sustained tumor regression.

AI summary of the abstract · may contain errors · not medical advice · read the paper.