Project description
A new target for cancer immunotherapy
Acyl CoA binding protein (ACBP) is a hormone that rises with ageing and can suppress immune defences. Higher blood levels are detected even before some cancers are diagnosed, suggesting an important role in disease development. The ERC-funded ACBP-DBI - Cancer project aims to develop a new antibody that blocks ACBP in both humans and mice. Researchers will test whether this antibody neutralises harmful ACBP signals, restores immune activity in human blood cells and improves anti tumour responses in mouse models of lung breast and soft tissue cancers. Success could support patents and launch new treatments for cancer and age-related diseases.
Objective
Acyl CoA binding protien (ACBP, encoded by diazepam binding inhibitor, DBI) is a novel glucocorticoid-induced tissue hormone that contributes to tissue aging. In still health individuals, the plasma concentrations of ACBP/DBI protein increase before cancer diagnosis. ACBP/DBI mediates immunosuppressive effects, meaning that its neutralization improves cancer immunosurveillance. Therefore, ACBP/DBI might be considered as an immune checkpoint. Thus far, we have demonstrated the immunostimulatory and cancer immunotherapeutic effects of ACBP/DBI inhibition by the inducible knockout of the Dbi gene or by means of a tool antibody recognizing mouse (but not human) ACBP/DBI protein.
Here, we propose the validation of an interspecies cross-reactive monoclonal antibody (mAb) recognizing an epitope that is shared among human and mouse ACBP/DBI. We plan to test this new (unpublished) antibody in three experimental settings: (i) the neutralization of human recombinant ACBP/DBI protein, abolishing its capacity to elict chloride fluxes via the GABAA receptor expressed by human cells; (ii) the reversal of the immunosuppressive effects of human recombinant ACBP/DBI protein or glucocorticoids (which transcriptionally induce ACBP/DBI) on primary human peripheral blood mononuclear cells; and (iii) the improvement of immunosurveillance and the reversal of immunosuppression by glucocorticoids in mouse models of non-small cell lung cancer, fibrosarcoma and breast cancer.
Altogether, these results should allow to file a composition-of-matter patent describing a therapeutically useful anti-ACBP/DBI mAb. Moreover, such data will increase the interest of potential investors in a yet-to-be-financed biotech company developing therapeutic anti-ACBP/DBI mAbs for the treatment of cancer and other age-related diseases.
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
- medical and health sciences clinical medicine oncology
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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
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-2025-POC
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75006 PARIS
France
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