TY  - JOUR
AU  - von Jutrzenka-Trzebiatowski, Alexandra
AU  - Gupte, Rutuja
AU  - Daglar, Cansu
AU  - Berndt, Nicole
AU  - Arndt, Claudia
AU  - Bachmann, Michael
AU  - Feldmann, Anja
TI  - CliniMACS Prodigy Manufacturing of Switchable, AND-Gate CAR T Cells.
JO  - International journal of molecular sciences
VL  - 26
IS  - 11
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - DKFZ-2025-01217
SP  - 5024
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Receptors, Chimeric Antigen: immunology
KW  - Receptors, Chimeric Antigen: metabolism
KW  - Receptors, Chimeric Antigen: genetics
KW  - Immunotherapy, Adoptive: methods
KW  - T-Lymphocytes: immunology
KW  - T-Lymphocytes: metabolism
KW  - CD28 Antigens: immunology
KW  - CD28 Antigens: genetics
KW  - CD3 Complex: immunology
KW  - CD3 Complex: genetics
KW  - Neoplasms: therapy
KW  - Neoplasms: immunology
KW  - Receptors, Antigen, T-Cell: genetics
KW  - Receptors, Antigen, T-Cell: immunology
KW  - Antigens, Neoplasm: immunology
KW  - CliniMACS Prodigy (Other)
KW  - RevCAR and Dual-RevCAR system (Other)
KW  - adapter CAR T cells (Other)
KW  - tumor therapy (Other)
KW  - Receptors, Chimeric Antigen (NLM Chemicals)
KW  - CD28 Antigens (NLM Chemicals)
KW  - CD3 Complex (NLM Chemicals)
KW  - Receptors, Antigen, T-Cell (NLM Chemicals)
KW  - Antigens, Neoplasm (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40507834
DO  - DOI:10.3390/ijms26115024
UR  - https://inrepo02.dkfz.de/record/302019
ER  -