Target intelligence / Profile preview

RQR8 cell surface safety switch (RQR8) (RQR8)

Target
RQR8
Molecular classification
Synthetic cell surface marker, Recombinant protein, Safety switch
01

Overview

RQR8 is a compact, synthetic cell surface molecule designed as a multi-functional tool for adoptive cell therapies, such as CAR-T cells (Philip et al., 2014, Blood). It integrates epitopes from CD34 and CD20 into a single construct, typically expressed alongside a therapeutic transgene. The CD34 epitopes allow for the enrichment and tracking of engineered cells using clinical-grade reagents like the QBEND/10 antibody (Vogler et al., 2022, Frontiers in Immunology). The CD20 mimotope serves as a safety switch, enabling the rapid depletion of the engineered cells through the administration of the monoclonal antibody Rituximab in the event of severe adverse effects like cytokine release syndrome. This dual-functionality provides a mechanism for both the manufacturing and the controlled termination of the cell therapy, enhancing the safety profile of highly potent immunotherapies. The construct is designed to be minimally immunogenic and highly efficient in its role as a suicide gene (Philip et al., 2014).

Other names
RQR8 marker geneRQR8 suicide geneCD34-CD20 chimeric markerRQR8 epitope
02

Mechanism of action

Rituximab-mediated depletion of RQR8-expressing cells via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (Philip et al., 2014).

03

Biological functions

Cell selectionCell depletionImmune response modulationCell tracking
04

Disease associations

CancerHematologic malignanciesB-cell lymphoma
05

Safety considerations

Incomplete depletion of engineered cellsPotential immunogenicity of the synthetic constructLoss of therapeutic cells upon Rituximab administration for unrelated reasons
06

Interacting drugs

Rituximab
07

Biomarkers

CD34 expressionCD20 mimotope expression

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