Objective
Adoptive T cell therapies have revolutionised cancer treatment in some haematological tumours. Despite astounding advances, patients often relapse because the transferred T cells have low persistence and they lose their effector function against cancer cells. The prime challenge for improving T cell therapies is to decipher the mechanisms that define T cell effector function and memory formation. The MA6TCELL project aims to disentangle this problem by defining how m6A methylation on mRNA regulates human CD8 T cell differentiation and function. m6A is the most abundant mRNA methylation and determines gene expression by regulating mRNA metabolism, altering as such cell function. Using the miCLIP assay, I previously mapped genome-wide the m6A sites on the mRNAs of human CD8 T cells (unpublished data I will provide the host with). This map revealed that m6A occurs not only at the known DRACH sequences, but also at AU-rich sequences (AREs). Intriguingly, the host has uncovered that AREs are critical regulators of cytokine production in memory CD8 T cells (host expertise). My pilot experiments revealed that chemical inhibition of a m6A demethylase in CD8 T cells decreased cytokine production, further supporting my hypothesis that m6A methylation controls CD8 T cell differentiation and function. To test this hypothesis the M6ATCELL project will: 1) define the regulatory mechanisms of m6A methylation in human CD8 T cell differentiation and effector function and 2) test whether m6A enzyme inhibitors improve the potency of CD8 T cell therapies using chimeric antigen receptor (CAR) T cells. Our findings will yield fundamental insights in T cell biology, which can be relevant for multiple adoptive T cell therapies. My long-term aim is to transfer my scientific findings from bench-to-bedside. Thus, I also secured a placement at the European Medicines Agency and if this proposal is granted, I will be trained on the regulatory guidelines of medicinal T cell products.
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 cell biology
- medical and health sciences clinical medicine oncology
- medical and health sciences medical biotechnology cells technologies
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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-MSCA-2022-PF-01
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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.
1006 AN Amsterdam
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.