Characterization of in vitro migratory properties of anti-CD19 chimeric receptor-redirected CIK cells for their potential use in B-ALL immunotherapy

Exp Hematol. 2006 Sep;34(9):1219-29. doi: 10.1016/j.exphem.2006.05.004.


Objective: Cytokine-induced killer (CIK) cells are ex vivo expanded cells enriched in CD3(+)CD56(+) natural killer T (NKT) cells with major histocompatibility-unrestricted cytotoxicity against several tumoral targets, except B-lineage acute lymphoblastic leukemia (B-ALL). We redirected CIK cells cytotoxicity toward B-ALL with a chimeric receptor specific for the CD19 antigen and then explored if modified-CIK cells maintain the same chemotactic properties of freshly isolated NKT cells, whose trafficking machinery reflects their preferential localization into the sites of B-ALL infiltration.

Material and methods: CIK cells were expanded ex vivo for 21 days and analyzed for expression of adhesion molecules and chemokine receptors regulating adhesion and homing toward leukemia-infiltrated tissues. CIK cells were then transduced with the anti-CD19-zeta-internal ribosomal entry site-green fluorescent protein retroviral vector and characterized for their cytotoxicity against B-ALL cells in a (51)Cr-release assay and for their trafficking properties, including chemotactic activity, adhesion and transendothelial migration, and metalloproteases-dependent invasion of Matrigel.

Results: Similarly to freshly isolated NKT cells, CD49d and CD11a were highly expressed on CIK cells. Moreover, CIK cells expressed CXCR4, CCR6, and CCR7 (mean expression 72%, 60%, and 32%, respectively), presenting chemotactic activity toward their respective ligands. Anti-CD19 chimeric receptor-modified CIK cells became cytotoxic against B-ALL cells (mean lysis, 60%) and showed, after exposure to a CXCL12 gradient, high capacity to adhere and transmigrate through endothelial cells and to invade Matrigel.

Conclusion: The potential capacity to localize into leukemia-infiltrated tissues of anti-CD19 chimeric receptor-redirected CIK cells, together with their ability to efficiently kill B-ALL cells, suggests that modified-CIK cells represent a valuable tool for leukemia immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / immunology
  • Antigens, CD19 / immunology*
  • Burkitt Lymphoma / immunology*
  • Burkitt Lymphoma / pathology
  • Burkitt Lymphoma / therapy
  • Cell Movement / genetics
  • Cell Movement / immunology*
  • Child
  • Child, Preschool
  • Cytotoxicity, Immunologic* / genetics
  • Female
  • Humans
  • Immunotherapy, Adoptive
  • K562 Cells
  • Killer Cells, Lymphokine-Activated / immunology*
  • Killer Cells, Lymphokine-Activated / transplantation
  • Leukemic Infiltration / immunology
  • Leukemic Infiltration / pathology
  • Male
  • Receptors, Chemokine / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation


  • Antigens, CD
  • Antigens, CD19
  • Receptors, Chemokine
  • Recombinant Fusion Proteins