title: Human CD80/IL2 lentivirus-transduced acute myeloid leukaemia (AML) cells promote natural killer (NK) cell activation and cytolytic activity: implications for a phase I clinical study.
abstract: Immunotherapeutic strategies may promote T and/or natural killer (NK) cell cytotoxicity. NK cells have the potential to exert a powerful anti-leukaemia effect, as demonstrated by studies of allogeneic transplantation. We have previously shown that CD80/interleukin 2 (IL2) lentivirus (LV)-transduced AML cells stimulate in-vitro T cell activation. The present study demonstrated that allogeneic and autologous culture of peripheral blood mononuclear cells with CD80/IL2-expressing AML cells also promoted NK cell cytotoxicity. Expression of the activation receptors NKp30, NKp44, CD244, CD25, CD69 and HLA-DR significantly increased following allogeneic culture and a consistent increased expression of NKp30, NKp44, NKp46, NKG2D, NKG2C and CD69, and up-regulation of the cytolytic marker CD107a was detected following autologous culture with LV-CD80/IL2 AML cells. Furthermore, increased NK cell lysis of K562 and primary AML blasts was detected. The lytic activity increased by twofold against K562 (from 46.6% to 90.4%) and allogeneic AML cells (from 11.8% to 20.1%) following in-vitro stimulation by CD80/IL2-expressing AML cells. More importantly for potential therapeutic applications, lysis of primary AML cells by autologous NK cells increased by more than 40-fold (from 0.4% to 22.5%). These studies demonstrated that vaccination of patients with CD80/IL2-transduced AML cells could provide a powerful strategy for T/NK cell-mediated stimulation of anti-leukaemic immunological responses.
authors.affiliation: Department of Haematological Medicine, King's College London, London, UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Ingram
authors.forename: Lucas
authors.initials: L
authors.lastname: Chan
authors.forename: Hayrettin
authors.initials: H
authors.lastname: Guven
authors.forename: David
authors.initials: D
authors.lastname: Darling
authors.forename: Shahram
authors.initials: S
authors.lastname: Kordasti
authors.forename: Nicola
authors.initials: N
authors.lastname: Hardwick
authors.forename: Linda
authors.initials: L
authors.lastname: Barber
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: Farzin
authors.initials: F
authors.lastname: Farzaneh
mesh_terms: D000328:Adult; D000368:Aged; D018122:B7-1 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000235:genetics*; D020014:K562 Cells; D016086:Lentivirus / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology*; D018709:Statistics, Nonparametric; D014161:Transduction, Genetic / Q000379:methods*; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D018122:B7-1 Antigen; D007376:Interleukin-2