title: Manipulating the expression of chemokine receptors enhances delivery and activity of cytokine-induced killer cells.
abstract: BACKGROUND
  Cytokine-induced killer (CIK) cells are ex vivo-expanded immune cells that express NK-cell and T-cell markers and that are routinely used in the treatment of many cancers. One key advantage of CIK cells is their ability to efficiently traffic to many solid tumours. Although likely to be mediated by chemokine receptor (CKR) expression, a thorough examination of the mechanism of tumour targeting has not been previously explored.
  
  
  METHODS
  Here, human CIK cell expansions were examined for the level, profile and kinetics of CKR expression.
  
  
  RESULTS
  It was found that CIK cells express a panel of CKRs, with considerable variation between donors. Importantly, CKR levels dropped considerably beyond 14 days in culture, being significantly reduced by day 28 (the time at which cytolytic activity peaked). As such, CIK preparations that are used clinically may not have optimal CKR expression. Several approaches were found to re-stimulate CKR cell-surface levels at these later time points. These approaches also enhanced cytolytic activity in vitro and were demonstrated to increase both in vivo tumour trafficking and anti-tumour activity in mouse models.
  
  
  CONCLUSIONS
  Simple modifications of the CIK expansion protocol could therefore be used to significantly enhance the anti-tumour effects of this therapy.
authors.affiliation: 1] Department of Surgey, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA [2] Institute of Clinical and Basic Medical Sciences, The First People's Hospital of Yunnan Province (The Kunhua Affiliated Hospital of Kunming University of Science and Technology), Kunming, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Surgey, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Hou
authors.affiliation: Department of Surgey, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Sampath
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1] Department of Surgey, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA [2] Department of Immunology, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Thorne
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D055612:Cytokine-Induced Killer Cells / Q000276:immunology / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism*
chemical_list: D019707:Receptors, Chemokine