Rapid generation of antigen-presenting cells from leukaemic blasts in acute myeloid leukaemia

Cancer Immunol Immunother. 2003 Jan;52(1):17-27. doi: 10.1007/s00262-002-0316-0. Epub 2002 Dec 7.

Abstract

The ability of acute myeloid leukaemia (AML) cells to acquire dendritic cell (DC)-like characteristics in vitro with a rapid culture method based either on the phorbol ester PMA or calcium ionophores has been studied in comparison to conventional AML-DC cultures with the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha), interleukin-3 (IL-3), SCF, FLT3-L and IL-4. In all AML patients, antigen-presenting cells (APC) could be generated from leukaemic cells in 2 days by incubation with PMA or calcium ionophore (A23187 or ionomycin) in the presence as well as in the absence of IL-4. In 30 out of 36 patients APC could be generated after 2 weeks of culture in cytokine-enriched medium. AML-APC cultured with PMA or calcium ionophores immunophenotypically and functionally were at a more mature stage than those cultured in cytokine-enriched medium. The most mature APC were generated by calcium ionophore A23187 plus IL-4, as evidenced by the higher expression of CD40, CD80, CD86 and HLA-DR. Autologous T cell mediated cytotoxicity towards AML blast cells in vitro was observed in 2 cases tested. The persistence of cytogenetic abnormalities confirmed the leukaemic origin of the AML-APC. The generation of AML-APC was possible from freshly isolated as well as cryopreserved material. Our data show that generation of sufficient AML-APC by A23187 plus IL-4 is feasible, for vaccination purposes, in approximately 70% of AML specimens, offering a time-saving and cost-effective approach in preparing anti-leukaemia vaccines.

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigen-Presenting Cells / cytology*
  • Antigen-Presenting Cells / immunology
  • Antigens, CD / biosynthesis
  • Antigens, Neoplasm / analysis
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • Calcimycin / pharmacology*
  • Calcium / physiology
  • Cancer Vaccines*
  • Cell Culture Techniques / methods*
  • Cryopreservation
  • Cytotoxicity, Immunologic
  • Feasibility Studies
  • Female
  • HLA-DR Antigens / biosynthesis
  • Humans
  • Interleukin-4 / pharmacology*
  • Ionophores / pharmacology
  • Leukemia, Myeloid / immunology*
  • Leukemia, Myeloid / pathology
  • Leukemia, Myeloid / therapy
  • Lymphocyte Culture Test, Mixed
  • Male
  • Middle Aged
  • Neoplastic Cells, Circulating / drug effects
  • Neoplastic Cells, Circulating / immunology
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / immunology
  • Reproducibility of Results
  • T-Lymphocytes, Cytotoxic / immunology
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Time Factors
  • Tissue Preservation / methods
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / immunology
  • Vaccination

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA-DR Antigens
  • Ionophores
  • Interleukin-4
  • Calcimycin
  • Tetradecanoylphorbol Acetate
  • Calcium