Objective
T cells engineered to express tumour-specific chimeric antigen receptors (CAR) proved effective against B-cell tumours. However, as the technology moves to solid cancers, clinical responses have not been as robust. In this setting, several barriers need to be overcome, including poor tumour recognition and a highly immunosuppressive tumour microenvironment (TME). Altered glycosylation is a hallmark of cancer, often manifesting as incomplete synthesis of O-glycans and increased branching of N-glycans. Glycosylation can mask epitopes to antibodies recognition and suppress anticancer immunity. My Unit was the first to report that N-glycans protect tumours from CAR-T cells and that pharmacological inhibition of N-glycosylation improves efficacy of CAR-T cell therapy in solid malignancies. With the aim of generating a single cell product able to safely offset multiple barriers of tumour resistance, I propose to engineer CAR-T cells to locally express an enzyme able to de-glycosylate tumour and TME cells. This goal will be achieved through the selection of a mutant able to deglycosylate the surface proteome of target cells. To regulate its function in CAR-T cells, I plan to test different systems based on the use of specific promoters, the inclusion of artificial miRNA target sequences, or the generation of a transmembrane variant. A deep characterization of the selected product will be performed in mice reconstituted with a human haemopoietic system. This model will allow to study the efficacy and safety of the proposed approach, and to assess its ability to remodel the TME toward a pro-inflammatory state. I believe that this project will have an immediate impact on cancer immunotherapy, will fuel the development of antiviral approaches and will provide new technological platforms. I have a deep knowledge of CAR-T cell therapy and have established a great network in the field. Despite ambitious, I believe I have the right skills and tools to make this project a reality.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine immunology immunotherapy
- 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.1.1 - European Research Council (ERC)
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-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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-STG
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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.
20132 Milano
Italy
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.