Descripción del proyecto
Producción de alto rendimiento de linfocitos T-CAR a partir de células madre
Las células madre pluripotentes inducidas (iPSC, por sus siglas in inglés) se obtienen a partir de células somáticas adultas a través de la reprogramación. Aunque se considera que constituyen una revolución médica y una fuente ilimitada de cualquier tipo de célula humana, la amplia aplicación de las iPSC con fines terapéuticos se ha visto obstaculizada por diversos problemas. El objetivo del proyecto NOVISTEM, financiado por el Consejo Europeo de Innovación, es agilizar la modificación genética de las iPSC y su posterior uso en terapia celular. Además, los investigadores utilizarán iPSC para generar linfocitos T con receptores de antígenos quiméricos para el antígeno (CAR) centrándose en una vía de señalización que impulsa el desarrollo de los linfocitos T. Esto les permitirá producir grandes cantidades de linfocitos T-CAR bien caracterizados para su uso clínico.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Tema(s)
Convocatoria de propuestas
HORIZON-EIC-2021-PATHFINDERCHALLENGES-01
Consulte otros proyectos de esta convocatoriaRégimen de financiación
HORIZON-EIC - HORIZON EIC GrantsCoordinador
9000 Gent
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