Project description
Nanobody-based reprogramming of the tumour vasculature to restore anti-tumour immunity
Harnessing the immune system to fight cancer is promising, but up to 80 % of non-small cell lung cancer patients do not respond or develop resistance to current therapies. These treatments often overlook endothelial cells, despite their emerging role in tumour immune evasion. The ERC-funded NANOBITER project builds on research that identified 26 immunosuppressive genes specific to endothelial cells, using AI tools and mouse models. NANOBITER aims to develop nanobody therapeutics targeting three of the most promising secreted or membrane-exposed targets. Expanding druggable targets beyond cancer and immune cells has shown potential to enhance anti-tumour immunity and slow tumour growth in laboratory studies. Project work could lead to more effective lung cancer treatments and a significant shift in cancer therapy.
Objective
"In non-small cell lung cancer (NSCLC), approximately 80% of patients have a poor response or develop resistance to current immunotherapies (IT), highlighting a critical need for more effective treatments. To date, most ITs focus on targeting cancer or immune cells, often overlooking endothelial cells (ECs), the body's largest organ. In the running ERC Adv Grant project MystIMEC (#101055155), we demonstrated the immunosuppressive nature of tumor ECs and their pathobiological role in tumor progression. With up to 90% of new drug candidates failing in clinical trials, often due to suboptimal target selection, the host lab has taken a fundamentally different approach to discovering novel therapeutic targets. Leveraging cutting-edge in-house developed AI and gene prioritization tools together with EC-selective lipid nanoparticle-based genetic silencing in a mouse lung tumor model, we discovered and validated 26 previously unexplored immunosuppressive genes (with poor functional annotation, ca 1/3 of human coding genome) as candidate therapeutic targets specific to ECs: silencing these genes promotes anti-tumor immune responses and reduces tumor growth. This ERC-PoC proposal builds further on these findings, aiming to develop nanobody (Nb) therapeutics for three promising targets with the greatest therapeutic efficacy. These targets are either secreted or membrane-exposed and therefore amenable to Nb-based inhibition, a treatment modality successfully used in the clinic. The results will provide the first Proof-of-Concept that our visionary approach to discover and validate unexplored immunosuppressive genes is an efficient, innovative, game-changing strategy. After generating Nbs, we will screen for the top two candidates with the strongest neutralizing effects in vitro (amongst other criteria). Finally, as Proof-of-Concept, the two selected Nbs will be validated in an in vivo lung tumor model for their efficacy to enhance anti-tumor immunity and to reduce tumor growth."
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 oncology lung cancer
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology immunotherapy
- natural sciences biological sciences genetics genomes
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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)
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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-2024-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.
9052 ZWIJNAARDE - GENT
Belgium
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