Objective
More than five decades have passed since asparagine depletion was developed into a successful therapy for childhood leukaemia. However, attempts to extend this treatment to other cancer types and amino acids were unsuccessful due to limited clinical benefit.
One of the most promising approaches for amino acid deprivation therapy leveraged the fact that most solid tumours (~70%) suppress intracellular arginine production, thereby becoming auxotrophic for arginine. However, although arginine deprivation monotherapies are well-tolerated and have been found to deplete arginine effectively, they have failed to benefit overall patient survival due to the development of treatment tolerance. Combinatorial therapies of arginine deprivation with chemotherapy and immunotherapy provided little advance.
Neoepitopes, defined as HLA-bound peptides derived from inducible tumour-specific aberrant proteins, offer an exciting new opportunity to overcome tolerance mechanisms. Using immunopeptidomics, we identified common neoepitopes emerging from arginine-deprived cancer cells. We further developed, validated, and characterized neoepitope-targeting T-cell receptors (TCRs) in vitro. We believe that these TCRs could be used to eliminate tumour cells before resistance to arginine deprivation emerges. However, due to the temporal expression of such neoepitopes, in vivo targeting remains a significant challenge, and a proof-of-concept experiment showing their in vivo utility is lacking.
This proposal aims to provide proof-of-concept mouse experiments for the in vivo application of combining arginine deprivation therapy with adoptive TCR T cell therapy targeting a shared and broadly expressed neoepitope induced by arginine deprivation. Ultimately, this innovative strategy aims to enhance the therapeutic efficacy of arginine deprivation and improve patient outcomes, offering a transformative approach to combat therapy resistance and enhance survival rates.
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
- medical and health sciences basic medicine immunology immunotherapy
- medical and health sciences clinical medicine oncology leukemia
- medical and health sciences medical biotechnology cells technologies
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Programme(s)
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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
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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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1066 CX Amsterdam
Netherlands
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