# STING & innate immune agonists

Source: https://onco.cc/technologies/sting-agonist/  
OnCo record `sting-agonist` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Drugs that trigger the cell's built-in 'virus alarm' inside tumours to summon immune cells.

## Summary

STING agonists are cyclic dinucleotide or non-nucleotide molecules that activate the STING to TBK1 to IRF3 axis, driving type I interferon and summoning immune cells into the tumour. In models this converts cold tumours, but intratumoural STING agonists (ADU-S100, MK-1454) disappointed in the clinic. Systemic and antibody-conjugated versions (TAK-500, XMT-2056), TLR9 agonists (vidutolimod), and CD40 agonists (sotigalimab) continue in trials as the next attempts. The cGAS-STING pathway also mediates the immune effects of radiation and ADCs, which is why the biology remains important even where the drugs have not worked. Weak clinical activity to date is the central open problem. The simple version is a drug that sets off the cell's built-in virus alarm inside the tumour.

## Fields

- Kind: Technology
- Status: phase-2
- Last checked: 2026-09-04
- Tags: frontier
- Principle: Cyclic dinucleotide or non-nucleotide agonists activate STING → TBK1 → IRF3 → type I interferon.
- Strengths: Converts cold tumours in models
- Limitations: Weak clinical activity to date

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Stimulator_of_interferon_genes
- Wikipedia: https://en.wikipedia.org/wiki/Stimulator_of_interferon_genes

## Connected records

- fronts: [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- pathways: [cGAS-STING innate sensing](https://onco.cc/pathways/cgas-sting/), [Cold tumours: immune deserts and exclusion](https://onco.cc/pathways/immune-desert-exclusion/), [The cancer-immunity cycle](https://onco.cc/pathways/cancer-immunity-cycle/)
- technologies: [Engineered bacteria as living cancer drugs](https://onco.cc/technologies/engineered-bacteria-therapy/), [Immune-stimulating antibody conjugate (ISAC)](https://onco.cc/technologies/immune-stimulating-adc/), [In situ vaccination](https://onco.cc/technologies/in-situ-vaccination/)
- terms: [Agonist and antagonist](https://onco.cc/terms/agonist-antagonist/), [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/)
- roadmaps: [Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity](https://onco.cc/roadmaps/immunotherapy-roadmap/)
- drugs: [ADU-S100 (MIW815)](https://onco.cc/drugs/adu-s100/)
- people: [Ronald Levy](https://onco.cc/people/ronald-levy/), [Thomas F. Gajewski](https://onco.cc/people/thomas-gajewski/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/)
- ideas: [Engineered bacteria that live in tumours and manufacture drugs there](https://onco.cc/ideas/idea-bio2-engineered-bacteria-payloads/), [Inhaled immune therapy to make the lung hostile to arriving tumour cells](https://onco.cc/ideas/idea-bio2-inhaled-lung-niche-immunotherapy/), [Make every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours](https://onco.cc/ideas/idea-moon-cold-to-hot-programme/), [Reprogramme the liver's own immune cells to refuse metastases](https://onco.cc/ideas/idea-bio2-liver-niche-kupffer-reprogramming/), [Turn one tumour into a vaccine to treat all the others](https://onco.cc/ideas/idea-bio2-in-situ-vaccination-solid/)
- institutions: [Harold C. Simmons Comprehensive Cancer Center, UT Southwestern](https://onco.cc/institutions/utsw-simmons/)

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