title: A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy.
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.
authors: UCL Cancer Institute, University College London, London, United Kingdom; and.
authors: Brian
authors: B
authors: Philip
authors: UCL Cancer Institute, University College London, London, United Kingdom; and.
authors: Evangelia
authors: E
authors: Kokalaki
authors: UCL Cancer Institute, University College London, London, United Kingdom; and.
authors: Leila
authors: L
authors: Mekkaoui
authors: UCL Cancer Institute, University College London, London, United Kingdom; and.
authors: Simon
authors: S
authors: Thomas
authors: UCL Cancer Institute, University College London, London, United Kingdom; and.
authors: Karin
authors: K
authors: Straathof
authors: UCL Cancer Institute, University College London, London, United Kingdom; and.
authors: Barry
authors: B
authors: Flutter
authors: Department of Pediatrics, Centro di Ricerca Matilde Tettamanti, University of Milano-Bicocca, Milan, Italy.
authors: Virna
authors: V
authors: Marin
authors: UCL Cancer Institute, University College London, London, United Kingdom; and.
authors: Teresa
authors: T
authors: Marafioti
authors: UCL Cancer Institute, University College London, London, United Kingdom; and.
authors: Ronjon
authors: R
authors: Chakraverty
authors: UCL Cancer Institute, University College London, London, United Kingdom; and.
authors: David
authors: D
authors: Linch
authors: UCL Cancer Institute, University College London, London, United Kingdom; and.
authors: Sergio A
authors: SA
authors: Quezada
authors: UCL Cancer Institute, University College London, London, United Kingdom; and.
authors: Karl S
authors: KS
authors: Peggs
authors: UCL Cancer Institute, University College London, London, United Kingdom; and.
authors: Martin
authors: M
authors: Pule
mesh_terms: D064591:Allografts; D000818:Animals; D018951:Antigens, CD20 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018952:Antigens, CD34 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*
chemical_list: D018951:Antigens, CD20; D018952:Antigens, CD34; D000939:Epitopes