Neoantigen Identification with Dendritic Cell Reprogramming

ended

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.