Descrizione del progetto
Una nuova immunoterapia basata sulle cellule B
I linfociti B manifestano diverse funzioni immunologiche, tra cui la produzione di anticorpi e la presentazione degli antigeni. Nuove prove indicano che queste cellule creano inoltre nicchie note come strutture linfoidi terziarie (TLS, tertiary lymphoid structure) associate alle cellule B, aggregati in grado di sostenere una risposta immunitaria. Il ruolo svolto dalle TLS nel cancro sta cominciando a essere chiarito solo ora, e la sua comprensione richiede ulteriori indizi sulla composizione cellulare e spaziale. Finanziato dal Consiglio europeo della ricerca, il progetto BeaT-IT intende determinare i fattori che stimolano le cellule B e inducono le TLS. I ricercatori impiegheranno nuovi biomateriali polimerici e testeranno diversi agenti e cellule allo scopo di verificarne la capacità di stimolare la formazione delle TLS. I materiali possono essere ulteriormente combinati con l’immunoterapia o la chemioterapia nel quadro di una strategia sinergica antitumorale.
Obiettivo
Recent clinical evidence points to a potential new direction in immuno-oncology: utilizing B cells and B cell-associated tertiary lymphoid structures (TLS). B cells display diverse immunological actions, including antibody production, antigen presentation, cytokine secretion and TLS induction. They have a dual role: they can initiate and reinforce anti-cancer immunity but B cells can also acquire regulatory phenotypes. To open up a new immunotherapeutic paradigm, I aim to understand how to optimally activate B cells, using nano-/biomaterials which load and precisely release a variety of agents to stimulate B cells and to suppress B cell regulatory phenotypes. Furthermore, I will manufacture porous scaffolds based on injectable microgels or via 3D printing with microgel fibers to induce TLS formation. The scaffolds with tunable porosity will allow B cells and other immune/stromal cells to infiltrate, arrange and expand, and soluble factors to diffuse. Moreover, the scaffolds can be easily functionalized with different chemical cues to stimulate B cells for TLS formation, such as CXC-chemokine ligand 13 and interleukin-7. This will help us understand TLS induction. Importantly, I will use ex vivo engineered TLS to study what microenvironmental factors influence their functionality. Subsequently, in vivo formation of B cell-associated TLS will be induced by the scaffolds. B cell activation and TLS induction will be combined for tumor therapy, and potential abscopal effect of the treatment to address metastases will be studied. The materials will be further combined with checkpoint inhibitors and chemotherapy to reach synergism. In addition, the new therapeutic strategies will be tested in patient-derived tumors established in humanized mice. BeaT-IT aims to understand optimal B cell activation and TLS formation with nano-/biomaterials to establish a new direction in immuno-oncology, which is anticipated to realize an upcoming breakthrough in cancer immunotherapy.
Campo scientifico
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.
- engineering and technologymaterials engineeringfibers
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicineimmunologyimmunotherapy
- engineering and technologymechanical engineeringmanufacturing engineeringadditive manufacturing
- engineering and technologyindustrial biotechnologybiomaterials
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-AG - HORIZON Action Grant Budget-BasedIstituzione ospitante
52074 Aachen
Germania