- Hydrogel retention alone is insufficient for in situ cancer vaccination: programmable spatiotemporal control, agonist pharmacology and antigen availability are essential.
- Mechanistic proof must include intracellular STING engagement, host-cell dependence, antigen cross-presentation, tumour-specific T-cell responses, immune memory and safety.
- Translation is limited by inconsistent mechanistic controls and human STING variability; propose indication-specific framework with matched comparators and spatial measurements.
Drug Discov Today. 2026 Nov 6:104851. doi: 10.1016/j.drudis.2026.104851. Online ahead of print.
ABSTRACT
Local hydrogels can sustain stimulator of interferon genes (STING) activation, but retention alone does not establish in situ cancer vaccination. This review evaluates STING-active hydrogels in postoperative, post-ablation, fibrotic, and regional tumor settings, emphasizing agonist pharmacology, antigen availability, tissue barriers, and spatiotemporal control. Non-hydrogel systems serve only as mechanistic comparators. We distinguish programmable behavior from passive release and assess intracellular engagement, host-cell dependence, antigen cross-presentation, tumor-specific T-cell responses, immune memory, and safety. Although selected murine studies show antitumor effects, inconsistent mechanistic controls and human STING variability constrain translation. We propose an indication-specific framework requiring matched comparators, spatial measurements, antigen-specific immunity, and human-relevant safety before claiming in situ vaccination.
PMID:42994583 | DOI:10.1016/j.drudis.2026.104851
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