RQR8 safety switch protein (RQR8)

RQR8 is a synthetic, compact chimeric protein designed as a multi-functional safety switch and marker gene for adoptive cell therapies, such as the BSB-1001 TCR-T cells developed by Biosyngen (Philip et al., Blood 2014). The construct is approximately 136 amino acids long and integrates epitopes from CD34 and CD20 into a single molecule expressed on the T-cell surface. Specifically, it contains a CD34 epitope for clinical-grade selection using the CliniMACS system and two CD20 mimotopes that provide a target for the monoclonal antibody Rituximab. In the context of BSB-1001, which targets EBV-associated antigens like LMP2A in nasopharyngeal carcinoma, RQR8 serves as a suicide gene to mitigate potential toxicities (Biosyngen, 2023). When Rituximab is administered to a patient, it binds to the RQR8-expressing T cells and triggers their elimination via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). This mechanism allows for the rapid termination of the therapy in the event of severe adverse reactions, such as cytokine release syndrome or off-target effects.

Other names

RQR8 suicide geneCD20-CD34-CD20 chimeric proteinRQR8 marker geneRQR8 safety switch

Rituximab binds to the CD20 mimotopes within the RQR8 construct expressed on the T-cell surface, inducing cell death through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).