Descrizione del progetto
Cellule artificiali con la funzione antitumorale delle cellule T
Le cellule T sono fondamentali nella difesa antitumorale, eppure le strategie di evasione dei tumori ne limitano l’efficacia. Decenni di ricerca si sono concentrati sullo sviluppo di terapie a base di cellule T a partire da cellule di donatori per il trattamento di tumori resistenti alla chemioterapia. Tuttavia, diversi fattori, quali considerazioni economiche ed effetti collaterali potenzialmente letali, ostacolano ancora il potenziale delle cellule T prelevate da donatori e ingegnerizzate contro i tumori. Finanziato dal Consiglio europeo per l’innovazione, il progetto ArTCell mira a superare queste limitazioni sviluppando cellule T artificiali che simulino le proprietà di riconoscimento e soppressione dei tumori delle cellule T. I ricercatori incorporeranno i componenti citotossici e di riconoscimento dei tumori delle cellule T attivate in vescicole a base lipidica per fornire un’alternativa più sicura, efficiente ed economica, eludendo le limitazioni che ostacolano un uso più ampio delle attuali terapie basate sulle cellule.
Obiettivo
T cells play a central role in anti-tumor immune protection. While their ability to target and eliminate emerging tumor cells is increasingly recognized, fully-established tumors can efficiently evade T cell response. Significant efforts spanning several decades of research have been made to develop T cell-based therapies manufactured from donor-derived T cells. The use of tumor-directed T cells engineered to express chimeric antigen receptors (CARs) represents, to date, one of the most successful applications for treatment of chemoresistant cancers. However, several major drawbacks, including economic factors, suboptimal functioning and life-threatening side effects, are still hindering the full potential of T cell-based therapies. To address this issue, we aim to generate Artificial T cells (ArTCell) that will mimic the anti-tumor function of a T cell-based therapy but in a safer, more efficient and less expensive product. ArTCells will incorporate two key features of activated T cells into Giant Unilamellar Vesicles (GUVs): the specificity of tumor cell recognition and the cytotoxic activity achieved through death ligands and cytolytic proteins. Functionalization of the GUVs will be confirmed by immunofluorescent labelling of membrane proteins (i.e. TRAIL, LFA-1 and CAR) and detection with flow cytometry. The morphology of ArTCell will be monitored via cryo-EM, SEM, and confocal microscopy. The ability of ArTCell to target and kill tumour cells will be thoroughly validated in vitro by a combination of functional and high resolution live imaging assays as well as in vivo with two cell line- and patient-xenografts mouse models. The ArTCell could allow to circumvent many of the current technological limitations that hinder a more wide-spread applicability of cell-based therapies, without being subject to tumor-mediated inactivation
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Invito a presentare proposte
HORIZON-EIC-2023-PATHFINDEROPEN-01
Vedi altri progetti per questo bandoMeccanismo di finanziamento
HORIZON-EIC - HORIZON EIC GrantsCoordinatore
3000 Leuven
Belgio