Project description
Not just blocking cancer, but removing its fuel
Most cancer drugs work by blocking harmful proteins, but some of the most crucial disease-causing proteins (especially those on the cell surface) are very hard to stop. The EIC-funded OutMARCH project aims to solve this by simply deleting them. Specifically, it will use specially engineered molecules called SureTACs that act by marking the cancer proteins as trash. This prompts the cell’s own recycling system to swallow the protein and break it down. Crucially, this strategy engages a selected class of enzymes that are highly active in tumours but quiet in the rest of the body. This means that the treatment could destroy hard-to-treat cancers, such as certain lymphomas, without affecting healthy tissue.
Objective
The OutMARCH project pioneers a paradigm-shifting protein degradation technology aimed at transforming the therapeutic landscape for cancer and beyond. By engineering a novel class of bispecific antibodies—SureTACs—that harness membrane-bound E3 ubiquitin ligases to selectively degrade disease-driving surface proteins. This groundbreaking lysosomal-targeting approach offers greater selectivity, durability, and breadth than conventional blocking therapies and, moreover, enables the targeting of previously 'undruggable' proteins. Central to our innovation is the utilization of the MARCH family of membrane-bound E3 ligases—an unconventional class of enzymes with remarkable substrate promiscuity and cancer-selective expression profiles. These properties make MARCH E3s ideal effectors for tissue-specific protein degradation, reducing off-target toxicity and overcoming treatment resistance. To unlock their therapeutic potential, we will develop a modular platform combining antibody engineering, innovative screening technologies, and machine-learning-guided design. The result will be a new class of biologics that direct the body’s own cellular machinery to dispose of harmful proteins.
Our initial focus is on two urgent oncology needs: therapy-resistant B-cell lymphomas and difficult-to-treat gastrointestinal cancers. Both cancer types rely on critical cell surface signaling hubs that evade traditional drug targeting. By degrading cancer-driving proteins at the cell surface, we aim to drive tumor-specific protein elimination to achieve durable anti-cancer effects. Using AI-guided antibody design and optimized E3-target pairing screens, OutMARCH will establish the first programmable, modular membrane degrader platform. While currently focused on oncology, this platform has broad potential across autoimmunity, transplantation, and chronic inflammation—paving the way for a new era of programmable degradation in precision medicine.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
- natural sciences biological sciences cell biology cell signaling
- medical and health sciences clinical medicine oncology
- medical and health sciences health sciences personalized medicine
- medical and health sciences basic medicine immunology immunotherapy
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.3.1 - The European Innovation Council (EIC)
MAIN PROGRAMME
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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.
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-EIC - HORIZON EIC 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) HORIZON-EIC-2025-PATHFINDEROPEN
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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.
3584 CX Utrecht
Netherlands
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.