Project description
Precision targeting of disease-causing immune cells in rheumatoid arthritis
Rheumatoid arthritis is a chronic autoimmune disease characterised by progressive joint damage and affects millions of individuals worldwide. The disease is caused when the immune system mistakenly attacks healthy joint tissue with antibodies produced by specific immune cells, leading to sustained inflammation. Current treatments involve broad immunosuppression, which increases infection risk and causes serious side effects. The ERC-funded PRECISION-RA project aims to develop a precision therapy that selectively destroys only the immune cells responsible for the pathology. Preliminary data indicates a high degree of cell specificity, preserving the remainder of the immune system. Preclinical validation in humanised animal models will support intellectual property development and pave the way for clinical trials.
Objective
Rheumatoid arthritis (RA) causes chronic pain and inflammation when the human immune system erroneously attacks healthy joint tissue. In over 70% of cases, B cells secrete anti-citrullinated protein antibodies (ACPAs), which are disease-causing autoreactive antibodies. Current treatments are focussed on dampening the whole immune system. These therapies can suppress or kill all B cells, not only the ACPA-secreting, autoreactive ones, leading to a compromised immune system, increased risk of infection and numerous severe side effects. These treatments are also not curative.
We have developed a method to target and kill only the ACPA-specific autoreactive B cells, leaving the rest of the B cell population, and human immune system, intact. This represents an exciting new treatment method for RA.
By capitalising on our deep understanding of human complement immunobiology and expertise in synthetic biology, we have developed a C1-activating bispecific (CAB). CAB comprises an engineered antibody fragment that binds to the first complement component, C1, which can induce cell killing when targeted to cell surfaces. We have conjugated CAB to a targeting moiety that directs complement to kill only B cells that secrete the autoreactive antibodies. Our preliminary data demonstrates remarkable cell specificity, as CAB destroys only the ACPA-specific autoreactive B cells in a large population of diverse cell types.
Here, we will apply our established protocols and expertise to generate important preclinical data, which includes humanised animal models to exemplify when and how CAB can be used to treat RA. This data will be used to strengthen our IP position, engage with clinical, industrial and patient stakeholders, and develop a robust business case to take CAB forward into clinical trials.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
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)
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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-POC - HORIZON ERC Proof of Concept Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-POC
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BS8 1QU BRISTOL
United Kingdom
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