Objective
DPP9 (dipeptidyl peptidase 9) is a cytosolic serine protease. It recognizes and cleaves N-terminal dipeptides containing proline at the penultimate position. The enzyme is currently receiving strong international attention after it was reported that DPP9 inhibition induces inflammatory cell death (pyroptosis) in Acute Myeloid Leukemia (AML) cells. Pyroptosis is a lytic form of cell death that also causes a pronounced, local upregulation of the innate immune system. This is of particular interest to leukemia treatment because the immune response to leukemic cells is strongly suppressed. Very recently, however, reports have been published that identify other, non-cancerous cell types that also undergo pyroptosis upon DPP9 inhibition. This raises questions on how selective and safe DPP9 inhibition can be as a therapeutic strategy in AML. The host reported the first selective, nanomolar DPP9 inhibitors in 2023 and also discovered the first DPP9-degrading PROTACs (unpublished data). PyroVectors mission is to selectively unleash these molecules pyroptosis induction potential against AML cells, by delivering them towards these cells with vector approaches. Given the general lack of knowledge on how to optimally target small molecules to AML cells, three molecules that recognize AML cells will be compared as vectors for DPP9 inhibitors: a monoclonal antibody, an AML cell-penetrating peptide, and a sialic acid analog. DPP9 inhibitors that are covalently linked to these 3 ligands, will be investigated in terms of internalization and pyroptosis induction in cells. Furthermore, AML selectivity and therapeutic potential in vivo will be characterized with the ultimate aim of validating the approach as a safe and effective therapeutic strategy for AML. Overall we are strongly convinced that this project can be an essential step toward a patient-friendly application of DPP9 inhibition or degradation in AML.
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.
- medical and health sciences clinical medicine oncology leukemia
- 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-2023-PF-01
See all projects funded under this callCoordinator
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.
2000 Antwerpen
Belgium
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.