Descrizione del progetto
L’immunoterapia del cancro trova la sua nicchia
L’attivazione di una risposta immunitaria ai patogeni dannosi richiede l’interazione di diversi tipi di cellule immunitarie. «Nicchie» specializzate presenti negli organi linfatici, nei siti di infiammazione e nei microambienti tumorali sono i siti di tale attività. ARTimmune sta progettando nicchie immunitarie sintetiche molto potenti per migliorare l’immunoterapia del cancro. Gli scienziati aumenteranno la comprensione delle interazioni cellulari nei linfonodi, portando alla progettazione mirata di potenti molecole immunomodulanti. Quindi, come commandos con potenti armi lasciate cadere su un bersaglio, le molecole verranno iniettate nei linfonodi insieme a un substrato che incoraggi l’infiltrazione di cellule immunitarie. Il potenziamento dell’attività immunitaria a livello locale potrebbe rivelarsi più efficace con molti meno effetti collaterali rispetto all’immunoterapia sistemica convenzionale, modificando le prognosi per milioni di pazienti affetti da cancro.
Obiettivo
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
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-ADG - Advanced GrantIstituzione ospitante
6525 GA Nijmegen
Paesi Bassi