PMID- 20139775 OWN - NLM STAT- MEDLINE DCOM- 20100614 LR - 20171116 IS - 1537-4513 (Electronic) IS - 1524-9557 (Linking) VI - 33 IP - 2 DP - 2010 Feb-Mar TI - Dendritic cells (DCs) can be successfully generated from leukemic blasts in individual patients with AML or MDS: an evaluation of different methods. PG - 185-99 LID - 10.1097/CJI.0b013e3181b8f4ce [doi] AB - 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. FAU - Kremser, Andreas AU - Kremser A AD - Medical Department III, University Hospital Grosshadern, Ludwig-Maximilians-University, 81377 Munich, Germany. FAU - Dressig, Julia AU - Dressig J FAU - Grabrucker, Christine AU - Grabrucker C FAU - Liepert, Anja AU - Liepert A FAU - Kroell, Tanja AU - Kroell T FAU - Scholl, Nina AU - Scholl N FAU - Schmid, Christoph AU - Schmid C FAU - Tischer, Johanna AU - Tischer J FAU - Kufner, Stefanie AU - Kufner S FAU - Salih, Helmut AU - Salih H FAU - Kolb, Hans Jochem AU - Kolb HJ FAU - Schmetzer, Helga AU - Schmetzer H LA - eng PT - Journal Article PL - United States TA - J Immunother JT - Journal of immunotherapy (Hagerstown, Md. : 1997) JID - 9706083 RN - 0 (Antigens, Differentiation) RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (Culture Media, Serum-Free) RN - 0 (Cytokines) RN - 39325-01-4 (Picibanil) RN - O84C90HH2L (Poly I-C) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antigen Presentation/drug effects MH - Antigens, Differentiation/metabolism MH - Antigens, Neoplasm/immunology/metabolism MH - *Cancer Vaccines MH - Cell Culture Techniques/*methods MH - Cell Differentiation/drug effects MH - Cell Separation MH - Culture Media, Serum-Free MH - Cytokines/metabolism/pharmacology MH - Cytotoxicity, Immunologic MH - Dendritic Cells/drug effects/immunology/metabolism/*pathology MH - Female MH - Flow Cytometry MH - Humans MH - Leukemia, Myeloid, Acute/immunology/*pathology/therapy MH - Male MH - Middle Aged MH - Myelodysplastic Syndromes/immunology/*pathology/therapy MH - Picibanil/pharmacology MH - Poly I-C/pharmacology MH - T-Lymphocytes, Cytotoxic/immunology EDAT- 2010/02/09 06:00 MHDA- 2010/06/15 06:00 CRDT- 2010/02/09 06:00 PHST- 2010/02/09 06:00 [entrez] PHST- 2010/02/09 06:00 [pubmed] PHST- 2010/06/15 06:00 [medline] AID - 10.1097/CJI.0b013e3181b8f4ce [doi] PST - ppublish SO - J Immunother. 2010 Feb-Mar;33(2):185-99. doi: 10.1097/CJI.0b013e3181b8f4ce.