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Engineered bacteria that live in tumours and manufacture drugs there

Some harmless bacteria naturally grow in the low-oxygen core of tumours. Engineering them to produce immune-activating drugs turns them into tiny factories inside the tumour.

Attenuated Salmonella and E. coli Nissle strains colonise hypoxic tumour cores selectively, and synthetic biology allows quorum-controlled payload release of STING agonists, CD47 nanobodies or cytokines. Early human experience with intratumoural bacterial therapy exists, and BCG in bladder cancer is a century-old proof that live bacteria can drive anti-tumour immunity. Safety, biocontainment and manufacturing are the real hurdles.

Hypothesis
A quorum-regulated engineered strain colonises human tumours at detectable levels after intravenous or intratumoural dosing and produces measurable local payload and immune activation without bacteraemia above grade 2.
Rationale
Tumour hypoxia is a selectivity handle that no small molecule can match, and payload release can be genetically gated to bacterial density inside the lesion. Escalating dose is a colonisation problem rather than a plasma exposure problem.
What would test it
First-in-human intratumoural dosing in accessible lesions with quantitative colonisation, payload and safety endpoints, plus a documented kill-switch demonstration.
Maturity
preclinical evidence
Who has to act
industry
Cost to try
Medium ($1M to $50M)
Years to first evidence
9
Bottlenecks it attacks

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