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Open Access Green as soon as Postprint is submitted to ZB.
Dendritic cells (DCs) can be successfully generated from leukemic blasts in individual patients with AML or MDS: An evaluation of different methods.
J. Immunother. 33, 185-199 (2010)
Myeloid-leukemic cells (AML, MDS, CML) can be differentiated to leukemia-derived dendritic cell [DC (DCleu)] potentially presenting the whole leukemic antigen repertoire without knowledge of distinct leukemia antigens and are regarded as promising candidates for a vaccination strategy. We studied the capability of 6 serum-free DC culture methods, chosen according to different mechanisms, to induce DC differentiation in 137 cases of AML and 52 cases of MDS. DC-stimulating substances were cytokines ("standard-medium", "MCM-Mimic", "cytokine-method"), bacterial lysates ("Picibanil"), double-stranded RNA ["Poly (I:C)"] or a cytokine bypass method ("Ca-ionophore"). The quality/quantity of DC generated was estimated by flow cytometry studying (co) expressions of "DC"antigens, costimulatory, maturation, and blast-antigens. Comparing these methods on average 15% to 32% DC, depending on methods used, could be obtained from blast-containing mononuclear cells (MNC) in AML/MDS cases with a DC viability of more than 60%. In all, 39% to 64% of these DC were mature; 31% to 52% of leukemic blasts could be converted to DCleu and DCleu-proportions in the suspension were 2% to 70% (13%). Average results of all culture methods tested were comparable, however not every given case of AML could be differentiated to DC with 1 selected method. However performing a pre-analysis with 3 DC-generating methods (MCM-Mimic, Picibanil, Ca-ionophore) we could generate DC in any given case. Functional analyses provided proof, that DC primed T cells to antileukemia-directed cytotoxic cells, although an anti-leukemic reaction was not achieved in every case. In summary our data show that a successful, quantitative DC/DCleu generation is possible with the best of 3 previously tested methods in any given case. Reasons for different functional behaviors of DC-primed T cells must be evaluated to design a practicable DC-based vaccination strategy.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
dendritic cells; myelodysplastic syndromes; acute myeloid leukaemia; immunotherapy; serum free culture
ISSN (print) / ISBN
1524-9557
e-ISSN
1537-4513
Journal
Journal of Immunotherapy
Quellenangaben
Volume: 33,
Issue: 2,
Pages: 185-199
Publisher
Lippincott Williams & Wilkins
Publishing Place
Philadelphia
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CCG Hematopoetic Cell Transplants (IMI-KHZ)