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Mutagenic chemotherapy and inhibition of mismatch repair as a strategy to boost anti-tumor immune response

Objective

In colorectal cancer (CRC), the efficacy of immunotherapy is currently limited to a small subgroup of tumors characterized by mismatch repair (MMR) deficiency. Conversely, little or no clinical benefit has been shown in the large majority of CRCs with MMR proficiency, which are accordingly defined as immune-cold tumors. Determining how to turn an immune-cold into a hot (immunotherapy responsive) tumor remains a major scientific challenge and an unmet clinical need.
Building on our recent demonstration that cytotoxic agents can increase tumor mutational burden and induce an immunogenic MMR deficient (MMRd)-like profile in preclinical CRC models, we devised CHIMERA as an ERC-2025-PoC initiative. CHIMERA leverages a validated in vitro and in vivo workflow to assess a first-in-class MMR inhibitor in combination with rationally selected cytotoxic agents, with the objective of converting MMR proficient (MMRp) cold tumors into an immunotherapy-responsive hot state. The project translates concepts generated within the ERC-ADG into a development program that integrates available drugs with novel molecules, thereby extending immunotherapy applicability beyond the current MMRd subgroup. Ultimately, CHIMERA is designed to consolidate proof-of-concept evidence for an innovative therapeutic strategy, laying the foundation for subsequent clinical testing and broader patient benefit in immuno-oncology.

Fields of science (EuroSciVoc)

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Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

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

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2025-POC

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Host institution

UNIVERSITA DEGLI STUDI DI TORINO
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
Address
VIA GIUSEPPE VERDI 8
10124 TORINO
Italy

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Region
Nord-Ovest Piemonte Torino
Activity type
Higher or Secondary Education Establishments
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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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