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RNA-based cancer ImmunotheraPeutics to Enhance CROssPrimming

Objective

Cancer immunotherapy achieves unprecedented efficacy against a number of malignant diseases. Preclinical experiments in mouse models conclude that type-1 dendritic cells (cDC1) that present tumor antigens are an absolute requirement for most immunotherapy strategies to be efficacious, including those routinely applied to cancer patients at present. cDC1 cells are specialized in redirecting engulfed cell-associated antigens to the class I MHC antigen-presentation pathway in the context of IL-12 production and co-stimulation, at least when cDC1 cells are in the presence of moieties denoting viral infection. Such phenomena are key to prime anti-tumor T lymphocytes through a mechanism known as crosspriming. The RIPECROP project will test immunotherapy agents that enhance the numbers and performance of cDC1 in the tumor tissue microenvironment. The strategies will be based on mRNA constructs that will encode engineered forms of the cDC1 growth factor sFLT-3L, single-chain interleukin-12, cDC1 specific chemoattractants and bispecific costimulatory ligands targeted to surface proteins of cDC1 cells. The new therapeutic agents in the form of coding mRNAs will be expressed in vivo either intratumorally or using the mRNA-transferred liver as an internal biofactory to systemically produce the encoded proteins and their combinations. Innovative in-vivo screenings based on hydrodynamic gene transfer of the liver with various expression plasmids encoding heterodimerization systems will be performed to identify suitable new mRNA-based immunotherapeutic chimeric constructs to enhance antitumor T-cell crosspriming. Overall, a novel mRNA-based toolbox will be studied both in terms of anti-tumor efficacy and regarding the mechanisms of action, in such a manner, that crosspriming will become exploitable in combinatorial approaches for cancer immunotherapy.

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Keywords

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Programme(s)

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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.

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.

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-2023-ADG

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Host institution

FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA
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.

€ 2 411 500,00
Address
AVENIDA DE PIO XII 55
31008 Pamplona
Spain

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Region
Noreste Comunidad Foral de Navarra Navarra
Activity type
Research Organisations
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.

€ 2 411 500,00

Beneficiaries (2)

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