Project description
Combinatorial strategies to optimise TCR-T cell therapy targeting neoantigens
Non-small-cell lung cancer (NSCLC) accounts for over 80 % of lung cancer cases. Despite some success with immune checkpoint treatments, many patients either do not respond or develop resistance, emphasising the need for more effective strategies. To address this, the ERC-funded NeoCure project will leverage T cell receptor (TCR) engineering to target tumour-specific neoantigens. It has already identified two principal neoantigens from KRAS driver mutations (G12V and G12C) and isolated their cognate TCRs. Subsequently, the project has demonstrated a novel treatment that combines lymphodepleting chemotherapy with KRAS G12V-specific TCR-T cell therapy to improve neoantigen presentation and tumour killing. NeoCure now aims to assess other novel combinatorial therapies by coupling its KRAS-specific TCR-T cells with enhanced chemotherapeutic strategies and neoantigen-targeted mRNA vaccines.
Objective
"Non-small-cell-lung-cancer (NSCLC) remains one of the most lethal cancers (≈1.5 million deaths annually), and current treatments fail to achieve universal, lasting remissions. While immune checkpoint therapies have improved NSCLC outcomes, many patients either do not respond or relapse, underscoring an urgent need for new, more effective strategies. NeoCure directly addresses this need by harnessing T-cell receptor (TCR) engineering to target tumor-specific neoantigens. In our prior research (ERC#101094980), we identified two prevalent neoantigens from common KRAS driver mutations (G12V and G12C) and isolated their cognate TCRs, which specifically recognize and eliminate cancer cells bearing these mutations. Notably, these KRAS G12V/C mutations (in the context of HLA-A*03:01) occur in an estimated 120,000 new lung, colon, and pancreatic cancer cases each year, highlighting the broad impact and commercial potential of this targeted approach.
We have demonstrated a breakthrough combinatorial therapy: adding a lymphodepleting chemotherapy to KRAS G12V-specific TCR-T cell therapy significantly enhances neoantigen presentation and tumor killing. Building on this finding, NeoCure will evaluate novel combination treatments – pairing our KRAS-specific TCR-T cells with optimized chemotherapy regimens and neoantigen-targeted mRNA vaccines – in advanced humanized mouse models. This PoC is designed as a critical step toward clinical translation, aiming for complete tumor elimination in preclinical models. In parallel, we are executing key pre-commercialization activities to ensure a clear path to clinical application. These include engaging with regulatory authorities (FDA/EMA) to align with fast-track approval pathways, forging industry partnerships for co-development, and strengthening our intellectual property around the NeoCure TCRs and therapy platform. Through this comprehensive approach, NeoCure is positioned as a transformative innovation in cancer immunotherapy.
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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
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine immunology immunotherapy
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Programme(s)
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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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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants
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(opens in new window) ERC-2025-POC
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7610001 Rehovot
Israel
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