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Programmable ARTificial immune systems to fight cancer

Project description

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.

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

Coordinator

STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRUM
Net EU contribution
€ 2 500 000,00
Address
Geert grooteplein 10 zuid
6525 GA Nijmegen
Netherlands

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Region
Oost-Nederland Gelderland Arnhem/Nijmegen
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00

Beneficiaries (2)