title: Human interferon-alpha increases the cytotoxic effect of CD56(+) cord blood-derived cytokine-induced killer cells on human B-acute lymphoblastic leukemia cell lines.
abstract: OBJECTIVE
  Cytokine-induced killer (CIK) cells may represent a promising immunotherapy for the treatment of children with relapsing B-lineage acute lymphoblastic leukemia (B-ALL) following hematopoietic stem cell transplantation (HSCT). Therefore, we investigated the possibility of combining adoptive immunotherapy with CIK cells and human interferon-alpha (hIFN-α) in order to potentiate the cytotoxicity of CIK cells against B-ALL.
  
  
  METHODS
  Cord blood- derived CIK (CB-CIK) cells were differentiated, stimulated with phosphate-buffered saline (PBS) or hIFN-α, and tested for cytotoxic activity. We tested the anti-leukemic and graft-versus-host disease (GvHD) effects of CB-CIK cells in a human xenograft NOD/SCID/γc(-) (NSG) mouse model.
  
  
  RESULTS
  Bulk CB-CIK cells showed very moderate cytotoxic activity while the subpopulation of CD56(+) CB-CIK cells showed significant cytotoxic activity against B-ALL cells. hIFN-α significantly augmented the cytotoxicity of CD56(+)CB-CIK cells in vitro and induced signal transducer and activator of transcription-1 (STAT1) phosphorylation. In addition, CD56(+)CB-CIK cells could delay mouse mortality significantly in vivo, and this effect was enhanced significantly by hIFN-α (P = 0.022). Furthermore, unlike CB mononuclear cells or peripheral blood mononuclear cells (PBMC), CD56(+)CB-CIK cells, alone or stimulated with hIFN-α, caused either no GvHD or mild GvHD, respectively, when injected into sublethally irradiated NSG mice.
  
  
  CONCLUSIONS
  CD56(+)CB-CIK cells are effective cytotoxic agents against human B-ALL cell lines in vitro and possess anti-leukemic activity that is potentiated by hIFN-α in an NSG mouse model in vivo. These pre-clinical data support the testing of this immunotherapeutic approach in the clinic for the treatment of B-ALL.
authors.affiliation: CHU Sainte-Justine Research Center, Center of Cancerology Charles-Bruneau, Montreal, Quebec, Canada.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Durrieu
authors.forename: Joëlle
authors.initials: J
authors.lastname: Gregoire-Gauthier
authors.forename: Mame Massar
authors.initials: MM
authors.lastname: Dieng
authors.forename: François
authors.initials: F
authors.lastname: Fontaine
authors.forename: Françoise
authors.initials: F
authors.lastname: le Deist
authors.forename: Elie
authors.initials: E
authors.lastname: Haddad
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D055612:Cytokine-Induced Killer Cells / Q000187:drug effects / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology*; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D016898:Interferon-alpha; D037181:Lectins, C-Type; D050794:STAT1 Transcription Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; D000099192:CD69 Antigens