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bioRxiv · 10.64898/2026.06.26.734859

Viral capsid delivery of cGAMP enhances STING-dependent antitumor immune response

Huang, P.·Jo, Y.·Martin, H. S.·Luteijn, R. D.·Raulet, D. H.·Francis, M. B.
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Abstract

Therapies to activate the STING immune response pathway represent promising potential anticancer treatments. However, the native STING activating molecule, 2,3-cGAMP, is a poor drug candidate due to its susceptibility to nuclease degradation and its relatively poor cell uptake. In this study, we present a nanoscale delivery vehicle based on the bacteriophage MS2 virus-like particle that can both protect cGAMP and deliver it into cells to access and bind cytosolic STING. MS2-delivered cGAMP achieved greatly increased STING activation potency relative to both free cGAMP and a nuclease-resistant synthetic cGAMP analog. In an in vivo murine colon carcinoma model, MS2-cGAMP elicited significant and prolonged antitumor activity in a STING-dependent manner at 50-fold lower concentrations relative to free cGAMP and synthetic analogs. These results demonstrate that MS2 delivery of cGAMP can yield a highly potent STING agonist immunotherapy with in vivo anticancer activity.

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Huang, P., Jo, Y., Martin, H. S., Luteijn, R. D., Raulet, D. H., Francis, M. B.. 2026-07-01. Viral capsid delivery of cGAMP enhances STING-dependent antitumor immune response. https://doi.org/10.64898/2026.06.26.734859

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