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Advancing NANOmedicines to rewire tumoral MYeloid cells for next-generation cancer immunotherapies

Objective

Persistent inflammation during tumorigenesis drives myelopoiesis. Consequently, monocytes and granulocytes/neutrophils infiltrate the tumor microenvironment (TME) and differentiate into tumor-associated macrophages or myeloid-derived suppressor cells, creating an immune-suppressive microenvironment that hampers cytotoxic T cell function and limits immune checkpoint inhibitor (ICI) efficacy. ‘Reprogramming’ myeloid cells to adopt pro-inflammatory phenotypes is promising to restore immune function and enhance ICI responses. Lipid nanoparticles (LNPs) have emerged as a delivery platform for nucleic acids, as demonstrated by the mRNA-LNP COVID vaccines. Pioneering studies revealed that myeloid cells are robustly recruited to the vaccine injection site where they internalize mRNA-LNPs, leading to mRNA expression in monocytes. While nanoparticle (NP) transport into inflamed tissues and tumors has been attributed to ‘enhanced permeation/retention’ of the NPs, my recent findings, in an inflamed arthritis model, highlight a critical role of circulating myeloid cells in the active transport of intravenously injected LNPs. Therefore, I hypothesize that mRNA-LNPs can transfect tumor-infiltrating myeloid cells reversing immune-suppression. My-NANO will study interactions between myeloid cells and lipid-based NPs through the following objectives: (1) elucidating the role of myeloid cells in the transport of lipid-based NPs to tumors (WP1), (2) investigating how mRNA-LNPs influence innate immune responses/phenotype switches in myeloid cells (WP2) and (3) optimizing mRNA-LNP design for efficient/selective mRNA expression in myeloid cells (WP3). Based on this knowledge My-NANO will design mRNA-LNPs to restore the phagocytic function of myeloid cells by knocking out SIRP-1α or by generating CAR-macrophages to enhance tumor responses to ICIs (WP4). By employing state-of-the-art methodologies, My-NANO hopes to advance mRNA-LNPs as ‘myeloid cell therapeutics’ for cancer immunotherapy.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2025-COG

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Host institution

UNIVERSITEIT GENT
Net EU contribution

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.

€ 2 499 750,00
Address
SINT PIETERSNIEUWSTRAAT 25
9000 GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Higher or Secondary Education Establishments
Links
Total cost

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.

€ 2 499 750,00

Beneficiaries (1)

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