Project description
Cancer immunotherapy and dendritic cell reprogramming
Genetic mutations in tumour cells create new tumour antigens; however, cell heterogeneity, downregulation of antigen presentation and inhibition of immune cell infiltration result in immune escape. The EU-funded TrojanDC project aims to advance a cancer immunotherapy concept based on dendritic cell (DC) reprogramming and switching tumour cells into antigen-presenting cells (APCs). Project researchers identified the transcription factors for reprogramming mouse fibroblasts into DCs, providing a new strategy to reprogramme tumour cells into APCs. The current project will define optimal factors to reprogramme human fibroblasts into DCs employing a single-cell screen. Next, they will attempt to reprogramme mouse and human tumour cells into tumour-APCs followed by evaluation of their ability to present antigens to T-cells. The project merges cell reprogramming and cancer immunotherapy, creating an entirely new approach to cancer therapy.
Objective
An important hallmark of cancer is the ability to evade the immune system. Genetic mutations in tumor cells result in the accumulation of tumor antigens (TAs), however, increased cell heterogeneity, downregulation of antigen presentation or inhibition of immune cell infiltration allows immune surveillance evasion. For the first time, direct cell reprogramming offers exciting opportunities to overcome these challenges. My group has recently identified a combination of transcription factors (TFs) sufficient to reprogram mouse fibroblasts into antigen-presenting dendritic cells (DCs), providing a new strategy to set in motion antigen-specific immune responses. I hypothesize that a similar combination reprograms tumor cells into antigen presenting cells (APCs). This proposal aims to test a cancer immunotherapy concept based on DC reprogramming and endowed APC function in tumor cells.
The work will proceed in three steps. First, I will define optimal TF combinations and external cues to efficiently reprogram human fibroblasts into DCs employing an innovative single-cell screen. Then, I will reprogram mouse and human tumor cells into tumor-APCs followed by characterization of transcriptome, chromatin accessibility, surface peptidome and ability to present antigens to T cells. Finally, I will test whether reprogrammed cells mount an attack against tumors in mouse models. I will further test the hypothesis that intratumoral delivery of reprogramming factors elicits in vivo antigen presentation, immune cell recruitment and tumor regression.
The approach proposed here will combine DCs antigen processing and presenting abilities with the endogenous generation of TAs. The induction of DC identity in cancer cells with ability to present a constellation of TAs will open new research and therapeutic avenues. This project represents a pioneering contribution by merging cell reprogramming and cancer immunotherapy, paving the way for an entirely new approach to cancer gene therapy.
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 genetics RNA transcriptomes
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine immunology immunotherapy
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - 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.
ERC-COG - Consolidator Grant
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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-2019-COG
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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.
22100 Lund
Sweden
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.