Project description
Targeted drug delivery for colorectal cancer
Antibody-drug conjugates (ADCs) are advanced cancer therapies designed to deliver cytotoxic agents directly to tumour cells, reducing damage to healthy tissue. These therapies utilise molecular ‘linkers’ engineered to release the therapeutic payload exclusively within the tumour environment. However, current linkers are not always precise, leading to unwanted drug release and side effects. With the support of the Marie Skłodowska-Curie Actions programme, the NextGenADCL project aims to develop new linkers that are selectively activated by enzymes found specifically in colorectal cancer tumours. Using innovative methods to identify these enzymes directly from patient samples, researchers will design and test improved ADCs in laboratory models. The goal is to create safer, more effective targeted therapies for colorectal cancer patients.
Objective
Antibody-drug conjugates (ADCs) are an emerging class of therapeutic agents that enable the delivery of potent cytotoxic drugs to cancer cells via engineered antibodies that selectively bind to antigens on the cell surface. Most clinically approved ADCs use protease-cleavable linkers between the antibody and the drug, so the drug remains inactive until its cleavage by tumour-associated proteases (TAPs), enabling targeted cancer-cell killing while avoiding systemic toxicity. Despite recent progress, the lack of specificity in current ADC linkers can cause unwanted payload release in healthy tissue, leading to toxicity, intolerable dosing, and high clinical attrition rates. Particularly for colorectal cancer (CRC), one of the leading causes of cancer-related deaths worldwide, no CRC-specific ADC has yet been approved.
Here, we propose to develop ADC(s) bearing novel TAP-selective linkers that release the drug in the tumour microenvironment of CRC. To achieve this ambitious goal, this project builds on the powerful “Substrate Identification From Tissue Resection” (SIFTR) platform recently developed in the Tate lab, which enables the de novo discovery of novel TAP substrates directly from human patient tissue. The novel TAP- selective substrate sequence(s) will form the basis for the design of activity-based probes (ABPs) to identify the TAP(s) involved via chemical proteomics and orthogonal methods. Finally, the TAP-selective substrate(s) will inform the design of innovative ADC linker(s). The ADC(s) will be constructed and validated as a proof-of-concept in CRC-relevant cellular disease models. Novel linkers developed in this proposal will provide much-needed innovation in ADC linker technology and help ensure ADCs reach their therapeutic potential in CRC. Notably, newly identified TAPs may also have applications as therapeutic targets in their own right.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences clinical medicine oncology
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
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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.
SW7 2AZ London
United Kingdom
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.