Neoantigen Identification with Dendritic Cell Reprogramming

Introduction

In cancer, genetic mutations result in the 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.

NeoIDC Platform Vision

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.

Methodology

To achieve this, we will:

1. Identify tumor peptides presented on MHC class I and II by cDC1-reprogrammed cancer cells and validate immunogenicity in vivo.
2. Expand neoantigen-specific T cells by co-culture with reprogrammed cancer cells, sequence TCRs, and link them to cognate neoantigens.

This will facilitate the generation of potent cancer vaccines and tumor-reactive T cells for adoptive transfer.

Collaboration and Commercialization

Experimental activities with collaborators and clinicians will be coupled with exploitation plans, including partnership with Asgard Therapeutics, ensuring commercialization through:

• Generation of novel intellectual property (IP)
• Broad and targeted dissemination
• Establishment of a new start-up company

Conclusion

NeoIDC combines cDC1s' 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.