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Tuneable Conditional Control of Engineered Bacterial Therapeutics

Project description

Innovative platform controlling engineered bacteria in tumour therapy

Certain bacteria can target tumours and deliver therapeutic agents directly, offering a promising approach to cancer treatment. However, current engineered bacterial therapies lack precise control over timing and dosage, limiting their safety and effectiveness. The ERC-funded BACTOCONTROL project will develop a synthetic receptor platform to enhance control over engineered bacteria in cancer therapy. Researchers will use E. coli Nissle 1917, a probiotic strain with tumour-targeting properties, to test synthetic receptor responses in a 3D tumour spheroid model. In the second phase, the study will assess gene expression and therapeutic release in a tumour mouse model using cytolytic and immunotherapeutic agents. The findings could pave the way for reliable bacterial cancer therapies.

Objective

Engineered microbes are attractive platforms for the diagnosis and treatment of several diseases. For example, bacteria can selectively target tumors and are ideal vehicles for in situ delivery of therapeutic agents.
However, as of today, no engineered living bacterial therapeutics in clinical trials have the ability for conditional control of therapeutic activity. This lack of reliable control over the timing and dosage of effector molecule production limits the specificity, safety, and efficacy of current bacterial therapies.
In this project, I will use of a generalizable synthetic receptor platform to control the in vivo therapeutic activity of engineered bacteria using an externally administered molecules. As a proof of concept, I will use a receptor responding to a molecule found in the diet to control therapeutic release in tumors. I will use a safe probiotic, E. coli Nissle 1917, with demonstrated tumor targeting properties.
In a first research line, I will characterize the dose-response and kinetics of synthetic receptors implemented in bacteria colonizing an in vitro 3D tumor spheroids model. I will then evaluate the therapeutic activity of strains producing cytolytic molecules in response to external inducer.
In a second research line, I will characterize conditional control of gene expression and then therapeutic release in tumor mice model, using cytolytic and immunotherapeutic effectors.
My work will deliver robust, safe, and efficient frameworks for conditional control of bacterial cancer therapy. By enabling in situ drug delivery with a highly-precise dosage and timing, it will allow physicians and ultimately the patients to finely control bacterial therapeutic activity.
Because of its modularity my platform will be further engineerable to detect other conditional inducers. This system will be reusable for the treatment of many other pathologies, including autoimmune and infectious diseases.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2022-POC2

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data

Beneficiaries (1)

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