RQR8 safety switch (RQR8)

RQR8 is a synthetic, compact cell-surface protein engineered to serve as both a selection marker and a safety switch for adoptive cell therapies, such as CAR-T cells (Philip et al., 2014, Blood). It consists of a signal peptide, two CD20 mimotopes, and a CD34 epitope, all anchored to the cell membrane via a CD8 alpha stalk (Philip et al., 2014, Blood). The CD34 component enables the enrichment of transduced cells using clinical-grade selection tools like the QBEND10 antibody (Miltenyi Biotec). The CD20 epitopes are specifically designed to be recognized by the monoclonal antibody Rituximab, which is already widely used in clinical practice (Philip et al., 2014, Blood). When Rituximab is administered to a patient, it binds to the RQR8-expressing cells and triggers their destruction through immune-mediated mechanisms like antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (Vogler et al., 2017, Molecular Therapy). This provides a suicide switch to terminate the therapy in the event of severe adverse effects, such as cytokine release syndrome or neurotoxicity (Tasian et al., 2017, Blood). Because Rituximab also targets endogenous B cells, its use as a safety switch results in temporary B-cell aplasia, which is a manageable clinical side effect.

Other names

CD20-CD34-CD20 constructRituximab-sensitive safety switchRQR8 cell surface markerCD20 epitope within RQR8

Rituximab binds to the CD20 mimotopes within the RQR8 construct on the surface of engineered cells, inducing cell death via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).