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Neoantigen Identification with Dendritic Cell Reprogramming

Project description

Cancer neoantigen-based immunotherapy

Somatic mutations in cancer cells give rise to novel peptides that are not present in normal cells and are thus considered as non-self antigens by the immune system. As a result, these neoantigens can serve as therapeutic targets for cancer immunotherapy, offering the possibility for personalised treatment. The ERC-funded NeoIDC project aims to identify highly immunogenic tumour neoantigens and neoantigen-specific T-cell receptors, using a previously developed technique of dendritic cell reprogramming. The identified neoantigens will be tested for immunogenicity in vivo and the neoantigen-specific T-cells will be expanded for the development of potent cancer vaccines and adoptive T-cell therapies, respectively. Overall, this project will provide a foundation for developing personalised and effective cancer immunotherapies.

Objective

In cancer, genetic mutations result in production of tumor neoantigens restrictively expressed in transformed cells and serve as ideal molecular targets for cancer vaccines and adoptive T cell therapies. However, available methods for the identification of clinically relevant neoantigens driving potent anti-tumor immunity are highly inefficient. Thus, there is an urgent need for innovative solutions to identify powerful immunogenic neoantigens to unlock the full potential of immunotherapy and treat currently untreatable cancers.
The NeoIDC platform has the radical vision to use the type 1 conventional dendritic cell (cDC1) reprogramming technology, arising from the ERC-funded project TrojanDC, to directly identify highly immunogenic tumor neoantigens and neoantigen-specific T cell receptors (TCRs) for the development of powerful cancer vaccines and adoptive T cell therapies. To achieve this, we will firstly identify tumor peptides presented on MHC class I and II by cDC1-reprogrammed cancer cells and validate immunogenicity in vivo. Secondly, we will expand neoantigen-specific T cells by co-culture with reprogrammed cancer cells, sequence TCRs and link to cognate neoantigens. This will facilitate the generation of potent cancer vaccines and tumor-reactive T cells for adoptive transfer. Experimental activities with collaborators and clinicians will be coupled with exploitation plans including partnership with Asgard Therapeutics, ensuring commercialization by generation of novel IP, broad and targeted dissemination and a new start-up company.
NeoIDC combines cDC1’s antigen processing and presenting abilities with the unique mutational profile of cancer cells to enable the direct identification of immunogenic neoantigens and cognate TCRs. Ultimately, this project will enable the development of the next generation of neoantigen-based vaccines and adoptive T cell therapies and will set the stage for a new era of safe, personalized and effective cancer immunotherapies.

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Topic(s)

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2022-POC2

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Host institution

LUNDS UNIVERSITET
Net EU contribution

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.

€ 150 000,00
Address
Paradisgatan 5c
22100 Lund
Sweden

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Region
Södra Sverige Sydsverige Skåne län
Activity type
Higher or Secondary Education Establishments
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Total cost

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Beneficiaries (1)

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