%0 Journal Article
%A von Jutrzenka-Trzebiatowski, Alexandra
%A Gupte, Rutuja
%A Daglar, Cansu
%A Berndt, Nicole
%A Arndt, Claudia
%A Bachmann, Michael
%A Feldmann, Anja
%T CliniMACS Prodigy Manufacturing of Switchable, AND-Gate CAR T Cells.
%J International journal of molecular sciences
%V 26
%N 11
%@ 1422-0067
%C Basel
%I Molecular Diversity Preservation International
%M DKFZ-2025-01217
%P 5024
%D 2025
%X 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.
%K Humans
%K Receptors, Chimeric Antigen: immunology
%K Receptors, Chimeric Antigen: metabolism
%K Receptors, Chimeric Antigen: genetics
%K Immunotherapy, Adoptive: methods
%K T-Lymphocytes: immunology
%K T-Lymphocytes: metabolism
%K CD28 Antigens: immunology
%K CD28 Antigens: genetics
%K CD3 Complex: immunology
%K CD3 Complex: genetics
%K Neoplasms: therapy
%K Neoplasms: immunology
%K Receptors, Antigen, T-Cell: genetics
%K Receptors, Antigen, T-Cell: immunology
%K Antigens, Neoplasm: immunology
%K CliniMACS Prodigy (Other)
%K RevCAR and Dual-RevCAR system (Other)
%K adapter CAR T cells (Other)
%K tumor therapy (Other)
%K Receptors, Chimeric Antigen (NLM Chemicals)
%K CD28 Antigens (NLM Chemicals)
%K CD3 Complex (NLM Chemicals)
%K Receptors, Antigen, T-Cell (NLM Chemicals)
%K Antigens, Neoplasm (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40507834
%R 10.3390/ijms26115024
%U https://inrepo02.dkfz.de/record/302019