Project description DEENESFRITPL Cancer immunotherapy finds its niche Activating an immune response to harmful pathogens requires the interaction of several types of immune cells. Specialised 'niches' found in lymph organs, inflammation sites and tumour microenvironments are the sites of this activity. ARTimmune is engineering very powerful synthetic immune niches to enhance cancer immunotherapy. Scientists will increase understanding of cellular interactions in lymph nodes, leading to the targeted design of powerful immunomodulating molecules. Then, like commandos with powerful weapons dropped into a target, the molecules will be injected into the lymph nodes along with a scaffold that encourages immune cell infiltration. Locally enhancing immune activity could prove more effective with far fewer side effects than conventional systemic immunotherapy, changing the prognoses for millions of cancer patients. Show the project objective Hide the project objective Objective Immunotherapy has entered centre stage as a novel treatment modality for cancer. Notwithstanding this major step forward, toxicity and immunosuppression remain major obstacles, and illustrate the pressing need for more powerful and specific immunotherapies against cancer. To overcome these roadblocks, in ARTimmune, I propose to follow a radically different approach by developing local rather than systemic immunotherapies. Taking advantage of the architecture of a lymph node (LN), I aim to design fully synthetic immune niches to locally instruct immune cell function. I hypothesize that programmable synthetic immune niches, when injected next to a tumour, will act as local powerhouses to generate bursts of cytotoxic T cells for tumour destruction, without toxic side effects. Single cell transcriptomics on LN, obtained from patients that are vaccinated against cancer, will provide unique insight in communication within immune cell clusters and provide a blueprint for the intelligent design of synthetic immune niches. Chemical tools will be used to build branched polymeric structures decorated with immunomodulating molecules to mimic LN architecture. These will be injected, mixed with sponge-like scaffolds to provide porosity needed for immune cell infiltration. Programming of immune cell function will be accomplished by in vivo targeting- and proteolytic activation- of immunomodulators for fine-tuning, and to extend the life span of these local powerhouses. The innovative character of ARTimmune comes from: 1) novel fundamental immunological insight in complex communication within LN cell clusters, 2) a revolutionary new approach in immunotherapy, by the development of 3) injectable- and 4) programmable- synthetic immune niches by state-of-the-art chemical technology. When successful, it will revolutionize cancer immunotherapy, moving from maximal tolerable dose systemic treatment with significant toxicity to local low dose treatment in the direct vicinity of a tumour Fields of science medical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapy Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-ADG - ERC Advanced Grant Call for proposal ERC-2018-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Coordinator STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRUM Net EU contribution € 2 500 000,00 Address Geert grooteplein 10 zuid 6525 GA Nijmegen Netherlands See on map Region Oost-Nederland Gelderland Arnhem/Nijmegen Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRUM Netherlands Net EU contribution € 2 500 000,00 Address Geert grooteplein 10 zuid 6525 GA Nijmegen See on map Region Oost-Nederland Gelderland Arnhem/Nijmegen Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 STICHTING RADBOUD UNIVERSITEIT Participation ended Netherlands Net EU contribution € 0,00 Address Houtlaan 4 6525 XZ Nijmegen See on map Region Oost-Nederland Gelderland Arnhem/Nijmegen Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
