Project description
Heating up cold colorectal tumours
Colorectal cancer responds well to immunotherapy only in a small group of patients whose tumours have defects in DNA repair. Most cases retain normal repair systems and remain ‘immune-cold’ without the immune system effectively recognising or attacking them. The ERC-funded CHIMERA project aims to change this by converting resistant colorectal tumours into ‘hot’ tumours that can respond to immunotherapy. Researchers will test a new inhibitor of DNA mismatch repair, together with selected chemotherapy drugs, in laboratory and animal models. By increasing tumour mutations and immune visibility, CHIMERA seeks to expand immunotherapy to many more patients and prepare this strategy for clinical trials.
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)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology colorectal cancer
- medical and health sciences basic medicine immunology immunotherapy
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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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.
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.
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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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.
10124 Torino
Italy
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.