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RevCAR T-cells (Reverse Universal CAR T-cells) are a modular and switchable chimeric antigen receptor (CAR) T-cell platform designed to improve the safety and flexibility of adoptive cell immunotherapy. Developed by researchers at Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and TU Dresden, the RevCAR system utilizes a 'reverse' architecture compared to standard modular CARs. In this system, the T-cells are engineered to express a CAR containing an extracellular peptide epitope, typically E5B9 derived from the human nuclear La/SS-B protein. These T-cells remain inactive until a bispecific adapter molecule, known as a Target Module (RevTM), is administered. The RevTM bridges the RevCAR T-cell to a tumor-associated antigen (TAA) by binding simultaneously to the E5B9 epitope on the T-cell and the target antigen on the tumor cell. This design allows for precise control over T-cell activity, as the system can be rapidly 'switched off' by withdrawing the short-lived RevTM. Furthermore, the platform enables 'AND-gated' logic-gated targeting to increase tumor specificity and reduce on-target-off-tumor toxicities in solid tumors by requiring the presence of two different RevTMs for full T-cell activation.
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