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| Home > Publications database > CliniMACS Prodigy Manufacturing of Switchable, AND-Gate CAR T Cells. |
| Home > Publications database > CliniMACS Prodigy Manufacturing of Switchable, AND-Gate CAR T Cells. |
| Journal Article | DKFZ-2025-01217 |
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2025
Molecular Diversity Preservation International
Basel
Abstract: The Reverse Chimeric Antigen Receptor (RevCAR) system is an adapter CAR T cell technology that allows the precise tuning of T cell activity and, thus, improved safety management. RevCAR T cells recognize and eradicate tumor cells via a bispecific adapter molecule, termed the RevCAR Target Module (RevTM). To further reduce the risk of on-target off-tumor toxicities, Dual-RevCAR T cells can be employed. These cells harbor two different RevCAR constructs, with the signaling domain of either CD3zeta or CD28. Therefore, Dual-RevCAR T cells only exert their full function when both RevCAR constructs are triggered simultaneously upon recognition of two different tumor antigens via RevTMs, enabling a precise AND-gate targeting approach and rendering them highly interesting for clinical application. For this purpose, standardized and reproducible clinical-grade cell manufacturing is required, for which the CliniMACS Prodigy can be used. Here, we present that automated processing of RevCAR and Dual-RevCAR T cells via the CliniMACS Prodigy results in potent expansion, strong transduction, and a favorable phenotype for clinical application. Moreover, obtained cell products were highly functional in a strict RevTM-dependent manner for both monospecific and AND-gate targeting, clearly underlining their high potential for clinical application against various tumor entities.
Keyword(s): Humans (MeSH) ; Receptors, Chimeric Antigen: immunology (MeSH) ; Receptors, Chimeric Antigen: metabolism (MeSH) ; Receptors, Chimeric Antigen: genetics (MeSH) ; Immunotherapy, Adoptive: methods (MeSH) ; T-Lymphocytes: immunology (MeSH) ; T-Lymphocytes: metabolism (MeSH) ; CD28 Antigens: immunology (MeSH) ; CD28 Antigens: genetics (MeSH) ; CD3 Complex: immunology (MeSH) ; CD3 Complex: genetics (MeSH) ; Neoplasms: therapy (MeSH) ; Neoplasms: immunology (MeSH) ; Receptors, Antigen, T-Cell: genetics (MeSH) ; Receptors, Antigen, T-Cell: immunology (MeSH) ; Antigens, Neoplasm: immunology (MeSH) ; CliniMACS Prodigy ; RevCAR and Dual-RevCAR system ; adapter CAR T cells ; tumor therapy ; Receptors, Chimeric Antigen ; CD28 Antigens ; CD3 Complex ; Receptors, Antigen, T-Cell ; Antigens, Neoplasm
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