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Blood. 2014 Aug 21;124(8):1277-87. doi: 10.1182/blood-2014-01-545020. Epub 2014 Jun 26.

A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy.

Author information

1
UCL Cancer Institute, University College London, London, United Kingdom; and.
2
Department of Pediatrics, Centro di Ricerca Matilde Tettamanti, University of Milano-Bicocca, Milan, Italy.

Abstract

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.

PMID:
24970931
DOI:
10.1182/blood-2014-01-545020
[Indexed for MEDLINE]
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