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

Philip, B; Kokalaki, E; Mekkaoui, L; Thomas, S; Straathof, K; Flutter, B; Marin, V; ... Pule, M; + view all (2014) A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood , 124 (8) 1277 - 1287. 10.1182/blood-2014-01-545020.

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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.

Type: Article
Title: A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy
Location: United States
DOI: 10.1182/blood-2014-01-545020
Publisher version: http://dx.doi.org/10.1182/blood-2014-01-545020
Language: English
Additional information: This research was originally published in Blood. Philip, B; Kokalaki, E; Mekkaoui, L; Thomas, S; Straathof, K; Flutter, B; Marin, V. A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood. 2014;124:1277-1287. © the American Society of Hematology.
Keywords: Allografts, Animals, Antigens, CD20, Antigens, CD34, Epitopes, Genes, Transgenic, Suicide, Genetic Therapy, Mice, Mice, Inbred BALB C, Neoplasms, T-Lymphocytes
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1434191
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