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Quantification of ex vivo generated dendritic cells (DC) and leukemia-derived DC contributes to estimate the quality of DC, to detect optimal DC-generating methods or to optimize DC-mediated T-cell-activation-procedures ex vivo or in vivo

Leukemia volume 21, pages 1338–1341 (2007)Cite this article

There is a need for less intensive (post-remission) immunotherapies to maintain stable remissions in AML and at least stable diseases in MDS before or after stem cell transplantation (SCT). The significance of T cells to mediate cellular anti leukemic reactions has been demonstrated by donor-lymphocyte-infusion (DLI) therapy of relapsed AML,1 although not all of the patients treated respond to this therapy. Professional antigen-presenting cells like dendritic cells (DC) could be used to overcome this therapeutic resistance and (re)-activate antileukemia-directed allogeneic or autologous T cells.2 Leukemic blasts from AML patients can be converted to ‘leukemia-derived DC’ (‘DCleu’), as already shown by others and us, giving rise to cells expressing ‘DC-typical markers’ together with the clonal or cell surface ‘blast’ marker of the AML.3, 4 ‘MCM-MIMIC’ is a standard method (GM-CSF, IL-4, TNF-α, IL-1β, IL-6, prostaglandin E) to generate DC.

Apply this evaluation strategy, we are able to estimate the capability of different DC-generating methods to provide DC and especially their capability to differentiate leukemic blasts to ‘leukemia-derived DC’. In the case given in Figure 3, the DC were generated in MCM-Mimic. In parallel, the cells had been cultured in two other DC-differentiating media (Picibanil and Ca-Ionophore). Using the strategy described here, MCM-MIMIC could be defined as the optimal method in this case of AML to generate DC/DCleu. Moreover, the application of our evaluation strategy allows us to set up ex vivo or in vivo stimulation experiments using defined amounts of DCleu to stimulate for example, T or NK cells. In addition, the in vivo occurrence of DCleu in individual patients can be monitored. A variation of this method could be used in the DC generation from healthy or leukemic MNC by quantifying and differentiating mature (e.g. CD14-negative, DC-marker positive) from immature (CD14-positive, DC-marker positive) DC.

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  1. Department for Hematopoetic Transplantations, Med III, Klinikum Grosshadern, University of Munich, Munich, Germany

    H M Schmetzer, A Kremser, J Loibl, T Kroell & H-J Kolb

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Schmetzer, H., Kremser, A., Loibl, J. et al. Quantification of ex vivo generated dendritic cells (DC) and leukemia-derived DC contributes to estimate the quality of DC, to detect optimal DC-generating methods or to optimize DC-mediated T-cell-activation-procedures ex vivo or in vivo. Leukemia 21, 1338–1341 (2007). https://doi.org/10.1038/sj.leu.2404639

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