Journal
BLOOD
Volume 124, Issue 8, Pages 1277-1287Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2014-01-545020
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Funding
- Medical Research Council Clinician Scientist Fellowship
- European Union
- United Kingdom National Institute for Health Research University College London Hospital Biomedical Research Centre
- Cancer Research UK [12100, 15556] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0507-10370, CL-2009-18-011, NF-SI-0513-10144] Funding Source: researchfish
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A compact marker/suicide gene that utilizes established clinical-grade reagents and pharmaceuticals would be of considerable practical utility to T-cell cancer gene therapy. Marker genes enable measurement of transduction and allow selection of transduced cells, whereas suicide genes allow selective deletion of administered T cells in the face of toxicity. We have created a highly compact marker/suicide gene for T cells combining target epitopes from both CD34 and CD20 antigens (RQR8). This construct allows selection with the clinically approved CliniMACS CD34 system (Miltenyi). Further, the construct binds the widely used pharmaceutical antibody rituximab, resulting in selective deletion of transgene-expressing cells. We have tested the functionality of RQR8 in vitro and in vivo as well as in combination with T-cell engineering components. We predict that RQR8 will make T-cell gene therapy both safer and cheaper.
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