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Cambridge Team Builds Two-Part Prodrug That Activates STING Only Inside Tumors

Peer-reviewed results in Nature Chemistry show tumor-restricted STING activation in engineered animal models.

Overview

  • The system pairs a β‑glucuronidase‑uncaged version of the STING agonist MSA2 with a second inert component that combine only in the tumor microenvironment.
  • In zebrafish and mouse studies engineered to produce β‑glucuronidase, the active compound formed almost exclusively in tumors and spared liver, kidney, and heart.
  • The components were largely inactive on their own yet triggered the pathway at very low concentrations when assembled under tumor conditions.
  • Researchers designed the chemistry to favor rapid, selective coupling at disease sites to address the systemic inflammation that has limited STING agonists.
  • The approach remains preclinical, with the team proposing broader safety studies and potential application of the two-component concept to other potent therapies.