Project description
Novel drugs against cancer and inflammatory diseases
CXCR4 is a chemokine receptor implicated in several pathological conditions including cancer and viral infections. It is activated by CXCL12, which regulates cell adhesion to stroma and hematopoietic stem cell mobilisation, and also serves as a co-receptor for HIV entry into cells. The aim of the EU-funded EPI-X4Health project is to test the endogenous peptide EPI-X4 for its therapeutic potential against cancer and inflammatory diseases. EPI-X4 is a human serum albumin derivative previously identified by the scientific team to inhibit HIV. Researchers will screen new synthetic derivatives of EPI-X4 in animal models of disease.
Objective
Deregulation of CXCL12 signaling via the CXCR4 chemokine receptor plays a key role in many diseases, including cancer, rheumatoid arthritis, chronic inflammation and cardiovascular disorders. Thus, agents modulating CXCR4 signaling offer many prospects for therapeutic development. CXCR4 is also a major coreceptor for HIV entry. Thus, we used HIV as tool to screen peptide libraries encompassing the entire blood peptidome for novel CXCR4 ligands. This approach allowed the identification of a small fragment of human serum albumin as potent HIV inhibitor. Remarkably, this naturally occurring peptide, named EPI-X4 (Endogenous Peptide Inhibitor of CXCR4), blocks CXCL12/CXCR4 signaling and suppresses cancer cell migration and invasion. Preclinical studies in mice show that EPI-X4 mobilizes hematopoietic stem/progenitor cells and inhibits lung inflammation in an asthma model. Preliminary analyses suggest that EPI-X4 is more specific and better tolerated than Mozobiol® (AMD3100), the only CXCR4 antagonist approved for clinical application. Recently, we developed synthetic derivatives of EPI-X4 showing about three orders of magnitude improved potency against HIV as well as increased plasma stability. Key goals of this project are to determine the therapeutic potential of these improved derivatives against cancers (Aim 1) and inflammatory diseases (Aim 2) using established mouse models of colon carcinoma, osteosarcoma, glioblastoma, airway inflammation and dermatitis. These disorders were selected from the large number of CXCR4-linked diseases because no safe and effective treatment exists and since preclinical mouse models are available to determine whether EPI-X4 derived agents are more efficient and better tolerated than other compounds. In parallel to the experimental assessment of the therapeutic potential of these novel CXCR4 antagonists, we will perform market analyses and develop an IPR strategy to pave the way towards commercialization and future clinical application.
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 health sciences inflammatory diseases
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs
- natural sciences biological sciences biochemistry biomolecules
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- 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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H2020-EU.1.1. - EXCELLENT SCIENCE - 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.
ERC-POC - Proof of Concept 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-2018-PoC
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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.
89081 Ulm
Germany
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.