Projektbeschreibung
Hochdurchsatzproduktion von CAR-T-Zellen aus Stammzellen
Induzierte pluripotente Stammzellen (iPSZ) werden durch Reprogrammierung aus adulten somatischen Zellen gewonnen. Sie gelten weithin als medizinische Revolution und als unerschöpfliche Quelle für menschliche Zellen jeder Art. Doch ihre breite Anwendung zu therapeutischen Zwecken wird bislang noch durch diverse Herausforderungen erschwert. Das vom Europäischen Innovationsrat finanzierte Projekt NOVISTEM verfolgt das Ziel, die genetische Modifizierung von iPSZ und ihre anschließende Anwendung in der Zelltherapie zu optimieren. Die Forschenden werden darüber hinaus auf einen wichtigen Signalweg der T-Zell-Entwicklung abzielen, um aus iPSZ chimäre Antigen-Rezeptor-T-Zellen (CAR-T-Zellen) zu generieren. Diese Methode wird es ihnen ermöglichen, gut charakterisierte CAR-T-Zellen für die klinische Anwendung in großen Mengen zu erzeugen.
Ziel
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.
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Thema/Themen
Aufforderung zur Vorschlagseinreichung
HORIZON-EIC-2021-PATHFINDERCHALLENGES-01
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
HORIZON-EIC - HORIZON EIC GrantsKoordinator
9000 Gent
Belgien