Generation of Leukaemia-Derived Dendritic Cells (DC<sub>leu</sub>) to Improve Anti-Leukaemic Activity in AML: Selection of the Most Efficient Response Modifier Combinations

Generation of Leukaemia-Derived Dendritic Cells (DC<sub>leu</sub>) to Improve Anti-Leukaemic Activity in AML: Selection of the Most Efficient Response Modifier Combinations

Dendritic cells (DC) and leukaemia derived DC (DC<sub>leu</sub>) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated from mononuclear cells in vitro following standard DC/DC<sub>leu</sub>-generating protocols. With respect t...

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Bibliographic Details
Main Authors: Christoph Schwepcke, Lara Kristina Klauer, Diana Deen, Daniel Christoph Amberger, Zuzana Fischer, Fatemeh Doraneh-Gard, Carina Gunsilius, Annika Hirn-Lopez, Tanja Kroell, Johanna Tischer, Melanie Weinmann, Jan-Ole Werner, Andreas Rank, Christoph Schmid, Helga Maria Schmetzer
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:International Journal of Molecular Sciences
Subjects:
leukaemia derived DC
acute myeloid leukaemia
anti-leukaemic functionality
Online Access:https://www.mdpi.com/1422-0067/23/15/8333
Description
Summary:Dendritic cells (DC) and leukaemia derived DC (DC<sub>leu</sub>) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated from mononuclear cells in vitro following standard DC/DC<sub>leu</sub>-generating protocols. With respect to future clinical applications though, DC/DC<sub>leu</sub>-generating protocols specifically designed for application in a whole-blood-(WB)-environment must be established. Therefore, we developed ten new DC/DC<sub>leu</sub>-generating protocols (kits; Kit-A/-C/-D/-E/-F/-G/-H/-I/-K/-M) for the generation of DC/DC<sub>leu</sub> from leukaemic WB, containing calcium-ionophore, granulocyte-macrophage-colony-stimulating-factor (GM-CSF), tumour-necrosis-factor-alpha, prostaglandin-E<sub>1</sub> (PGE<sub>1</sub>), prostaglandin-E<sub>2</sub> (PGE<sub>2</sub>) and/or picibanil (OK-432). All protocols were evaluated regarding their performance in generating DC/DC<sub>leu</sub> using refined classification and/or ranking systems; DC/DC<sub>leu</sub> were evaluated regarding their performance in stimulating anti-leukaemic activity using a cytotoxicity fluorolysis assay. Overall, we found the new kits capable to generate (mature) DC/DC<sub>leu</sub> from leukaemic WB. Through refined classification and ranking systems, we were able to select Kit-I (GM-CSF + OK-432), -K (GM-CSF + PGE<sub>2</sub>) and -M (GM-CSF + PGE<sub>1</sub>) as the most efficient kits in generating (mature) DC/DC<sub>leu</sub>, which are further competent to stimulate immunoreactive cells to show an improved anti-leukaemic cytotoxicity as well. This great performance of Kit-I, -K and -M in mediating DC/DC<sub>leu</sub>-based anti-leukaemic immunity in a WB-environment in vitro constitutes an important and directive step for translating DC/DC<sub>leu</sub>-based immunotherapy of AML into clinical application.
ISSN:1661-6596
1422-0067

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