Project description
Cell-free tumour-derived immunotherapy
Extracellular vesicles (EVs) are cell-secreted particles employed for cell-to-cell communication and delivery metabolites, proteins, lipids, and nucleic acids. Although tumour-derived EVs (TEX) are known for their immunosuppressive function, emerging evidence suggests that cancer cells can modulate the biogenesis and content of TEX, potentially altering their impact on the immune system. Funded by the European Research Council, the IMMUNO-TEX project proposes to generate TEX as cell-free anticancer agents to stimulate anti-cancer immunity. Researchers will investigate the mechanisms by which TEX are loaded with specific cargo and exploit the cellular machinery to produce immunostimulatory TEX. The proposed work will overcome the limited effectiveness and resistance linked to certain immunotherapies.
Objective
Tumor immunotherapy with immune checkpoint inhibitors (ICI) has unprecedented therapeutic potential, but its success is limited to a minority of patients with preexisting antitumor T-cell immunity. For patients with poorly-immunogenic tumors, combinatorial immunotherapies are urgently needed. With a vast and bioactive cargo (proteins, lipids, nucleic acids), extracellular vesicles (EVs) have intrinsic property to regulate complex pathways in distant target cells. Even though they can transfer tumor antigens which potentially activate T cells, tumor-derived EVs (TEX) have mainly been associated with immunosuppressive function. I have recently identified innate immune pathways within tumor cells that regulate TEX biogenesis and immunogenicity. This allows for the first time to force tumor cells to release a defined immunostimulatory (is)TEX product. The unconventional objective of IMMUNO-TEX is to generate a platform for the pioneering therapeutic use of tumor-derived isTEX as multifunctional cell-free anticancer agents. isTEX combine a cargo of a plethora of patient-specific tumor (neo-) antigens and immunostimulatory constituents within a single, non-toxic delivery vehicle, that allows for efficient priming of tumor antigen-specific T cells. The ability to harness the vast potential of isTEX is directly interwoven with a more detailed mechanistic understanding how tumor-specific cargo packaging in EVs occurs and how they alter immune cell function. Therefore, IMMUNO-TEX will identify and exploit the intracellular machinery in tumor cells for optimal isTEX generation, investigate how isTEX enable an immune-supportive tumor microenvironment, and validate isTEX to overcome ICI resistance in relevant murine and human model systems. Hereby, IMMUNO-TEX will eliminate current limitations of ICI immunotherapy by rationally designed combination with isTEX to allow responsiveness in patients with poorly immunogenic tumors.
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.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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-ERC - HORIZON ERC Grants
See all projects funded under this funding scheme
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) ERC-2022-STG
See all projects funded under this callHost institution
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.
81675 MUENCHEN
Germany
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.