EPI-CART
Financiado
Understanding and exploiting epigenetic regulation in CAR T cell therapy
The dramatic efficacy of CAR T cell therapy in certain hematopoietic malignancies provides clinical validation of a groundbreaking paradigm: Human cells can be engineered into purpose-built therapeutic agents by genetically introd...
The dramatic efficacy of CAR T cell therapy in certain hematopoietic malignancies provides clinical validation of a groundbreaking paradigm: Human cells can be engineered into purpose-built therapeutic agents by genetically introducing artificial regulatory programs. The EPI-CART project will focus on epigenetic regulation in CAR T cell therapy – an important but underappreciated aspect of all cell-based therapies.
We will investigate the regulatory dynamics during CAR T cell therapy in unprecedented molecular detail, by following 40 patients who will receive treatment for two blood cancers (Aim 1). Using single-cell epigenome/transcriptome profiling of CAR T cells and sequential biopsies, clonal tracking, monitoring of immune regulation, and liquid biopsies, we will bioinformatically reconstruct patient-specific trajectories, identify molecular markers for therapy monitoring, and uncover epigenetic drivers of CAR T cell response.
To engineer the first epigenetically boosted CAR T cells for hard-to-treat cancers (CAR-T-resistant blood cancers, solid tumors), we developed a CAR T cell screening/engineering platform that enables us to functionally test thousands of potential regulators in cellular assays and mouse tumor models (Aim 2). The in vivo experiments leverage our CRISPR single-cell sequencing method (CROP-seq), supporting rational optimization of CAR T cells and quantitative modeling of the underlying regulatory mechanisms.
The EPI-CART project will uncover key roles of epigenetic regulation in CAR T cells, advance our understanding of existing CAR T cell therapies, and establish new approaches for areas with unmet clinical need. We will establish preclinical proof-of-concept for the efficacy of epigenetically boosted CAR T cells and provide a compelling rationale for subsequent first-in-human clinical trials. More generally, this project will demonstrate the biological roles and translational potential of epigenetic programs in cell-based therapy.
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Duración del proyecto: 68 meses
Fecha Inicio: 2021-03-30
Fecha Fin: 2026-11-30
Fecha Fin: 2026-11-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2021-03-30
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2020-COG:
ERC CONSOLIDATOR GRANTS
Cerrada
hace 4 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
CEMM FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZ...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
350.00K€ |
Participante