Summary
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.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101071105 |
| Start date: | 01-11-2022 |
| End date: | 31-10-2026 |
| Total budget - Public funding: | 3 871 287,50 Euro - 3 644 418,00 Euro |
Cordis data
Original description
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.Status
SIGNEDCall topic
HORIZON-EIC-2021-PATHFINDERCHALLENGES-01-03Update Date
09-02-2023
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