Descrizione del progetto
Produzione ad alte prestazioni di cellule T del recettore dell’antigene chimerico da cellule staminali
Le cellule staminali pluripotenti indotte (iPSC) hanno origine dalla riprogrammazione di cellule somatiche adulte. Sebbene siano considerate una vera e propria rivoluzione medica e una fonte illimitata di qualsiasi tipo di cellula umana, l’ampia applicazione delle iPSC a fini terapeutici è stata ostacolata da diverse problematiche. Finanziato dal Consiglio europeo per l’innovazione, il progetto NOVISTEM mira a semplificare la modifica genetica delle iPSC e il loro successivo utilizzo nella terapia cellulare. Inoltre, i ricercatori utilizzeranno le iPSC per generare cellule T del recettore dell’antigene chimerico (CAR), puntando su una via di segnalazione che stimola lo sviluppo delle cellule T. Ciò consentirà di produrre un gran numero di cellule CAR-T ben caratterizzate per l’uso clinico.
Obiettivo
Despite the increasing awareness that cell and gene-therapy approaches have tremendous biomedical potential, their broad clinical application has been challenging due to prolonged and expensive production times and the emergence of severe immune- and gene-delivery dependent side effects. In this proposal, we aim to establish a stream-lined and high-throughput protocol for iPSC-based cell therapy by combining a novel technological platform for gene delivery with a breakthrough biological concept that will permit to manufacture functional, gene-corrected blood forming stem cells and CAR T cells. To achieve this, we will use and optimize photoporation as non-viral gene delivery method for CRISPR-mediated and site-specific gene-editing to obtain controlled CAR expression and for performing gene-correction in iPSCs. From these gene-modified iPSCs, we will generate CAR T cells and blood forming stem cells, respectively, by selectively targeting a signaling pathway that we established to be critical in human blood cell development and particularly T cell development. Following functional validation of the generated cell products, we will optimize the current protocols to increase the potential for clinical implementation and establish a high-throughput photoporation platform to generate a large number of CAR expressing iPSC lines from different ages, sex and ethnicities to demonstrate the population-wide implementation potential of our approach. This will allow to generate a bank of well-characterized, HLA-defined CAR expressing iPSC that can be used as of-the-shelf cell therapy products, thereby significantly advancing the currently implemented adaptive CAR T cell approaches by reducing the production costs and time, by selectively targeting the CAR into a well-controlled location which will prevent variability and by facilitating the production and evaluation of novel CARs for other cancer entities such as solid tumors.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Argomento(i)
Invito a presentare proposte
HORIZON-EIC-2021-PATHFINDERCHALLENGES-01
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HORIZON-EIC - HORIZON EIC GrantsCoordinatore
9000 Gent
Belgio