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Inflaming the microenvironment of colorectal cancer to enable immunotherapy

Objective

Microsatellite-stable colorectal cancer (MSS CRC) accounts for 85–90% of CRCs and remains largely resistant to immune checkpoint blockade (ICB), one of the most transformative advances in oncology. Consequently, the majority of patients with advanced CRC cannot benefit from immunotherapy, representing a major unmet clinical need. INFLAME-TME proposes a novel strategy to overcome this limitation by converting immunologically “cold” MSS tumors into ICB-responsive lesions through targeted induction of tumor-intrinsic immunogenic stress.
Building on discoveries from the ERC AdG PLASTICAN, we identified a previously unrecognized target that is responsible for mitotic spindle assembly while its downregulation causes chromosome missegregation, micronucleus formation, and activation of the cGAS/STING innate immune pathway. In preclinical models of MSS CRC, depletion induces strong CD8⁺ T cell infiltration and sensitizes tumors to ICB. To translate this discovery into a therapeutic strategy, we developed a targeted RNA-based approach aiming to impair tumor cell division while triggering innate immune activation within the tumor microenvironment. INFLAME-TME will assess the technical feasibility and translational potential of this strategy. Key objectives include validating mitotic disruption and cGAS/STING activation, evaluating ICB sensitization, and defining the intellectual property, regulatory, and commercialization paths for further development.
If successful, INFLAME-TME will establish a new paradigm in cancer immunotherapy where targeted RNA delivery induces tumor-intrinsic immunogenicity to overcome ICB resistance. Beyond CRC, this concept could open opportunities for RNA-based immunomodulatory therapies across diverse immunotherapy-resistant malignancies.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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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-2026-POC

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Host institution

CHEMOTHERAPEUTISCHES FORSCHUNGSINSTITUT GEORG-SPEYER-HAUS STIFTUNG
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
PAUL EHRLICH STRASSE 42-44
60596 FRANKFURT
Germany

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Region
Berlin Berlin Berlin
Activity type
Research Organisations
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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)