Project description
First-in-class P2Y6 biological blockers to treat pancreatic cancer
Immunotherapy has revolutionised cancer treatment, yet pancreatic cancer remains a challenge. Previous ERC CoG ImmunoFit research identified metabolic pathways that drive immunosuppression in the tumour microenvironment, with recent findings highlighting the CDA-UDP-P2Y6 axis as a key factor in pancreatic cancer’s immune evasion. The ERC-funded PA-PYR-us project will build on these insights to develop first-in-class P2Y6 biological blockers. It will investigate metabolic interactions between cancer and immune cells, focusing on the UDP-elicited, P2Y6-dependent pathway as a target for triggering strong antitumour responses with minimal side effects or resistance. Additionally, the project will assess existing small-molecule inhibitors of P2Y6 and demonstrate the need for innovative approaches to develop new targeting molecules in vivo.
Objective
The introduction of immunotherapy revolutionized cancer treatment, nevertheless, pancreatic cancer is still an omen of death with a dismal 5-year survival rate. Improvement of the current therapies for pancreatic cancer patients is thus an unmet medical need.
The research we performed for the ERC CoG ImmunoFit identified novel metabolic pathways shaping the tumor microenvironment toward immunosuppression. Our latest publication in Nature Cancer characterized the CDA-UDP-P2Y6 axis as a major determinant of pancreatic cancer immune escape. With this PoC grant, we want to start the valorization of our findings, generating first-in-class P2Y6 biological blockers.
Characterization of the metabolic crosstalk between cancer cells and the immune infiltrate, identified the UDP-elicited, P2Y6-dependent pathway as the most promising target to induce strong anti-tumor response and immunotherapy sensitization at minimal risk of side effects and generation of resistance. Evaluation of the current landscape of small molecules available for P2Y6 inhibition highlighted the urgent need for an out-of-the-box approach to generate a new class of molecules suitable to target this pyrimidine receptor in vivo.
Here, we will take advantage of the specific know-how present in our host institute to generate (in collaboration with the VIB drug discovery center) VHH nanobody blockers.
The feasibility of this ambitious project is ensured by (I) the strong results supporting the scientific rationale, (II) the compelling freedom-to-operate analysis, (III) the keen evaluation of the landscape of competitors as well as (IV) the presence of an outstanding experience, within our institution, on GPCR-targeting nanobody generation.
With this application, we aim to start the generation and validation of P2Y6 biological blockers and file a “composition of matter” patent application to foster the further clinical development of our identified lead.
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.
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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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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.
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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-ERC-POC - HORIZON ERC Proof of Concept Grants
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Call for proposal
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(opens in new window) ERC-2024-POC
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9052 ZWIJNAARDE - GENT
Belgium
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