Project description
Long-lasting specific depletion of autoreactive B-cells to cure autoimmune diseases
Most incurable human autoimmune diseases are chronic conditions characterised by the presence of autoantibodies. Elimination of the autoreactive B-cells are not presently feasible due to a lack of specific markers. The EU-funded Target to B-cure project aims to develop a vaccine that will allow specific long-lasting depletion of autoreactive B-cells. Using autoimmune rheumatoid arthritis (RA) as a model, it will study the RA-specific autoimmune response. Researchers will identify autoreactive B-cells and the B-cell receptor (BCR) repertoire at several stages of the disease to determine the potency of the non-germline-encoded mutations in BCRs as antigens amenable to T-cell recognition and vaccination. Finally, the project will design patient-tailored vaccines and perform a phase I trial to determine the feasibility of depleting disease-causing B-cells.
Objective
Currently, most human autoimmune diseases are chronic conditions without a prospect of cure. My aim in this proposal is to meet the next major challenge, achieving cure in autoimmune disease.
Many autoimmune diseases are characterized by autoantibodies and are remarkably responsive to B-cell targeted therapies, demonstrating that the autoreactive B-cell is central to disease pathogenesis. Nonetheless, the selective and permanent elimination of the autoreactive B-cell, both memory and plasma cells alike, is not presently feasible due to a lack of specific markers and treatments. My aim is to develop a vaccine that will allow the specific and long-lasting depletion of autoreactive B-cells, thereby inducing cure. Using the unique mutated sequences of autoreactive B-cell receptors (BCR), cytotoxic T-cells that specifically eradicate autoreactive B-cells will be induced. This concept extends the remit of vaccines beyond infectious diseases and cancer, into the sphere of autoimmune disease.
Using the well-defined autoimmune disease rheumatoid arthritis (RA) as prototype, I will study the RA-specific autoimmune response. Our recent findings show that RA is characterized by a restricted, oligoclonally-expanded autoreactive B-cell pool. Using recently developed technologies, my team will identify autoreactive B-cells and the BCR repertoire at several (pre)disease stages. We will then determine the potency of the many non-germline-encoded mutations in BCRs as neoantigens amenable to T-cell recognition and vaccination. Incorporating these neoantigens into multiple long peptides covering the autoreactive B-cell repertoire, we will design patient-tailored vaccines and perform a phase I trial to determine the feasibility of specifically depleting disease-causing B-cells.
This research will create the possibility for patient-tailored vaccines that can permanently eradicate auto-reactive B-cells in B-cell driven auto-immune diseases; diseases that are still incurable to date.
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.
- medical and health sciences clinical medicine rheumatology
- natural sciences biological sciences biochemistry biomolecules
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
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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-ADG - Advanced 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-ADG
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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.
2333 ZA Leiden
Netherlands
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.