Rapid generation of antigen-presenting cells from leukaemic blasts in acute myeloid leukaemia.
Cancer Immunol Immunother
; 52(1): 17-27, 2003 Jan.
Article
em En
| MEDLINE
| ID: mdl-12536236
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
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Acetato de Tetradecanoilforbol
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Leucemia Mieloide
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Calcimicina
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Interleucina-4
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Técnicas de Cultura de Células
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Vacinas Anticâncer
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Células Apresentadoras de Antígenos
Limite:
Aged80
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article