title: Assessment of the effector function of CMV-specific CTLs isolated using MHC-multimers from granulocyte-colony stimulating factor mobilized peripheral blood.
abstract: BACKGROUND
  Adoptive transfer of CMV-specific T cells has shown promising results in preventing pathological effects caused by opportunistic CMV infection in immunocompromised patients following allogeneic hematopoietic stem cell transplantation. The majority of studies have used steady-state leukapheresis for CMV-reactive product manufacture, a collection obtained prior to or months after G-CSF mobilization, but the procurement of this additional sample is often not available in the unrelated donor setting. If the cellular product for adoptive immunotherapy could be generated from the same G-CSF mobilized collection, the problems associated with the additional harvest could be overcome. Despite the tolerogenic effects associated with G-CSF mobilization, recent studies described that CMV-primed T cells generated from mobilized donors remain functional.
  
  
  METHODS
  MHC-multimers are potent tools that allow the rapid production of antigen-specific CTLs. Therefore, in the present study we have assessed the feasibility and efficacy of CMV-specific CTL manufacture from G-CSF mobilized apheresis using MHC-multimers.
  
  
  RESULTS
  CMV-specific CTLs can be efficiently isolated from G-CSF mobilized samples with Streptamers and are able to express activation markers and produce cytokines in response to antigenic stimulation. However, this anti-viral functionality is moderately reduced when compared to non-mobilized products.
  
  
  CONCLUSIONS
  The translation of Streptamer technology for the isolation of anti-viral CTLs from G-CSF mobilized PBMCs into clinical practice would widen the number of patients that could benefit from this therapeutic strategy, although our results need to be taken into consideration before the infusion of antigen-specific T cells obtained from G-CSF mobilized samples.
authors.affiliation: Oncohematology Research Group, Navarrabiomed - Miguel Servet Foundation, IDISNA (Navarra's Health Research Institute), Irunlarrea 3, 31008, Pamplona, Spain. lorea.beloki@gmail.com.
authors.forename: Lorea
authors.initials: L
authors.lastname: Beloki
authors.affiliation: Oncohematology Research Group, Navarrabiomed - Miguel Servet Foundation, IDISNA (Navarra's Health Research Institute), Irunlarrea 3, 31008, Pamplona, Spain. miriam.ciaurriz.gortari@cfnavarra.es.
authors.forename: Miriam
authors.initials: M
authors.lastname: Ciaurriz
authors.affiliation: Oncohematology Research Group, Navarrabiomed - Miguel Servet Foundation, IDISNA (Navarra's Health Research Institute), Irunlarrea 3, 31008, Pamplona, Spain. cristina.mansilla.puerta@cfnavarra.es.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mansilla
authors.affiliation: Oncohematology Research Group, Navarrabiomed - Miguel Servet Foundation, IDISNA (Navarra's Health Research Institute), Irunlarrea 3, 31008, Pamplona, Spain. amaya.zabalza.sanmartin@cfnavarra.es.
authors.forename: Amaya
authors.initials: A
authors.lastname: Zabalza
authors.affiliation: Oncohematology Research Group, Navarrabiomed - Miguel Servet Foundation, IDISNA (Navarra's Health Research Institute), Irunlarrea 3, 31008, Pamplona, Spain. estela.perez.valderrama@cfnavarra.es.
authors.forename: Estela
authors.initials: E
authors.lastname: Perez-Valderrama
authors.affiliation: Department of Haematology, University College London Medical School, University College London, London, UK. edward.samuel@ucl.ac.uk.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Samuel
authors.affiliation: Department of Haematology, University College London Medical School, University College London, London, UK. m.lowdell@ucl.ac.uk.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lowdell
authors.affiliation: Oncohematology Research Group, Navarrabiomed - Miguel Servet Foundation, IDISNA (Navarra's Health Research Institute), Irunlarrea 3, 31008, Pamplona, Spain. nramireh@cfnavarra.es.
authors.forename: Natalia
authors.initials: N
authors.lastname: Ramirez
authors.affiliation: Oncohematology Research Group, Navarrabiomed - Miguel Servet Foundation, IDISNA (Navarra's Health Research Institute), Irunlarrea 3, 31008, Pamplona, Spain. eduardo.olavarria.lopez@cfnavarra.es.|Department of Haematology, Complejo Hospitalario de Navarra, Navarra Health Service, IDISNA (Navarra's Health Research Institute), Pamplona, Spain. eduardo.olavarria.lopez@cfnavarra.es.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Olavarria
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000187:drug effects / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D053804:Granzymes / Q000378:metabolism; D006680:HLA Antigens / Q000378:metabolism*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D010455:Peptides / Q000276:immunology; D010641:Phenotype; D055503:Protein Multimerization; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006680:HLA Antigens; D018836:Inflammation Mediators; D010455:Peptides; D016179:Granulocyte Colony-Stimulating Factor; D053804:Granzymes