title: CCR7+selected gene-modified T cells maintain a central memory phenotype and display enhanced persistence in peripheral blood in vivo.
abstract: Adoptive T cell immunotherapy (ATCT) for cancer entails infusing patients with T cells that recognise and destroy tumour cells. Efficient engraftment of T cells and persistence in the circulation correlate with favourable clinical outcomes. T cells of early differentiation possess an increased capacity for proliferation and therefore persistence, using these cells for ATCT could therefore lead to improved clinical outcomes.
  
  
  
  We describe a method to enrich T cells of early differentiation status using paramagnetic beads and antibodies targeting cells expressing C-C motif chemokine receptor 7 (CCR7).
  
  
  
  Selection of cells expressing CCR7 enriches T cells of bearing markers of early differentiation status. This was validated through analysis of an array of surface markers and an observed reduction in effector cell functions ex vivo. CCR7 selection resulted in dramatic 83.6 and 137 fold increases in circulating levels of CD4 and CD8 T cells respectively compared to non-sorted T cells 3 weeks after adoptive transfer to NSG mice. We observed no significant difference in the engraftment levels of CCR7 or CD62L selected cells in the NSG mouse model. Comparison of cells ex vivo, however, suggests CCR7 selection is superior to CD62L selection in enriching T cells of early differentiation status.
  
  
  
  CCR7 selection offers a means to enrich T cells of early differentiation status for ACTC. Together our data suggests that these T cells are likely to display enhanced engraftment and persistence in patients in vivo and could therefore improve therapeutic efficacy of ACTC.
authors.affiliation: Clinical and Experimental Immunotherapy Group, Manchester Cancer Research Centre, Faculty of Biology, Medicine and Health, Division of Cancer Sciences, The University of Manchester, Wilmslow Road, Withington, Manchester, M20 4QL UK.
authors.forename: Gray
authors.identifier: 0000-0001-9066-0181
authors.initials: G
authors.lastname: Kueberuwa
authors.affiliation: Clinical and Experimental Immunotherapy Group, Manchester Cancer Research Centre, Faculty of Biology, Medicine and Health, Division of Cancer Sciences, The University of Manchester, Wilmslow Road, Withington, Manchester, M20 4QL UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: Gornall
authors.affiliation: Clinical and Experimental Immunotherapy Group, Manchester Cancer Research Centre, Faculty of Biology, Medicine and Health, Division of Cancer Sciences, The University of Manchester, Wilmslow Road, Withington, Manchester, M20 4QL UK.
authors.forename: Erik Marcelo
authors.initials: EM
authors.lastname: Alcantar-Orozco
authors.affiliation: Clinical and Experimental Immunotherapy Group, Manchester Cancer Research Centre, Faculty of Biology, Medicine and Health, Division of Cancer Sciences, The University of Manchester, Wilmslow Road, Withington, Manchester, M20 4QL UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Bouvier
authors.affiliation: Clinical and Experimental Immunotherapy Group, Manchester Cancer Research Centre, Faculty of Biology, Medicine and Health, Division of Cancer Sciences, The University of Manchester, Wilmslow Road, Withington, Manchester, M20 4QL UK.
authors.forename: Zainul Abedin
authors.initials: ZA
authors.lastname: Kapacee
authors.affiliation: Clinical and Experimental Immunotherapy Group, Manchester Cancer Research Centre, Faculty of Biology, Medicine and Health, Division of Cancer Sciences, The University of Manchester, Wilmslow Road, Withington, Manchester, M20 4QL UK.
authors.forename: Robert Edward
authors.initials: RE
authors.lastname: Hawkins
authors.affiliation: Clinical and Experimental Immunotherapy Group, Manchester Cancer Research Centre, Faculty of Biology, Medicine and Health, Division of Cancer Sciences, The University of Manchester, Wilmslow Road, Withington, Manchester, M20 4QL UK.
authors.forename: David Edward
authors.initials: DE
authors.lastname: Gilham
mesh_terms: D000818:Animals; D006801:Humans; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D020014:K562 Cells; D051379:Mice; D010641:Phenotype; D054400:Receptors, CCR7 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*
chemical_list: C515370:CCR7 protein, human; D054400:Receptors, CCR7
keywords: Adoptive cell therapy; CCR7; CD62L; Central memory; DMF5; Differentiation status; Immunotherapy; Transgenic TCR