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

Dendritic cells (DC) and leukaemia derived DC (DC(leu)) 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(leu)-generating protocols. With respect to future clinical applications though, DC/...

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Autores principales: Schwepcke, Christoph, Klauer, Lara Kristina, Deen, Diana, Amberger, Daniel Christoph, Fischer, Zuzana, Doraneh-Gard, Fatemeh, Gunsilius, Carina, Hirn-Lopez, Annika, Kroell, Tanja, Tischer, Johanna, Weinmann, Melanie, Werner, Jan-Ole, Rank, Andreas, Schmid, Christoph, Schmetzer, Helga Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368668/
https://www.ncbi.nlm.nih.gov/pubmed/35955486
http://dx.doi.org/10.3390/ijms23158333
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author Schwepcke, Christoph
Klauer, Lara Kristina
Deen, Diana
Amberger, Daniel Christoph
Fischer, Zuzana
Doraneh-Gard, Fatemeh
Gunsilius, Carina
Hirn-Lopez, Annika
Kroell, Tanja
Tischer, Johanna
Weinmann, Melanie
Werner, Jan-Ole
Rank, Andreas
Schmid, Christoph
Schmetzer, Helga Maria
author_facet Schwepcke, Christoph
Klauer, Lara Kristina
Deen, Diana
Amberger, Daniel Christoph
Fischer, Zuzana
Doraneh-Gard, Fatemeh
Gunsilius, Carina
Hirn-Lopez, Annika
Kroell, Tanja
Tischer, Johanna
Weinmann, Melanie
Werner, Jan-Ole
Rank, Andreas
Schmid, Christoph
Schmetzer, Helga Maria
author_sort Schwepcke, Christoph
collection PubMed
description Dendritic cells (DC) and leukaemia derived DC (DC(leu)) 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(leu)-generating protocols. With respect to future clinical applications though, DC/DC(leu)-generating protocols specifically designed for application in a whole-blood-(WB)-environment must be established. Therefore, we developed ten new DC/DC(leu)-generating protocols (kits; Kit-A/-C/-D/-E/-F/-G/-H/-I/-K/-M) for the generation of DC/DC(leu) from leukaemic WB, containing calcium-ionophore, granulocyte-macrophage-colony-stimulating-factor (GM-CSF), tumour-necrosis-factor-alpha, prostaglandin-E(1) (PGE(1)), prostaglandin-E(2) (PGE(2)) and/or picibanil (OK-432). All protocols were evaluated regarding their performance in generating DC/DC(leu) using refined classification and/or ranking systems; DC/DC(leu) 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(leu) from leukaemic WB. Through refined classification and ranking systems, we were able to select Kit-I (GM-CSF + OK-432), -K (GM-CSF + PGE(2)) and -M (GM-CSF + PGE(1)) as the most efficient kits in generating (mature) DC/DC(leu), 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(leu)-based anti-leukaemic immunity in a WB-environment in vitro constitutes an important and directive step for translating DC/DC(leu)-based immunotherapy of AML into clinical application.
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spelling pubmed-93686682022-08-12 Generation of Leukaemia-Derived Dendritic Cells (DC(leu)) to Improve Anti-Leukaemic Activity in AML: Selection of the Most Efficient Response Modifier Combinations Schwepcke, Christoph Klauer, Lara Kristina Deen, Diana Amberger, Daniel Christoph Fischer, Zuzana Doraneh-Gard, Fatemeh Gunsilius, Carina Hirn-Lopez, Annika Kroell, Tanja Tischer, Johanna Weinmann, Melanie Werner, Jan-Ole Rank, Andreas Schmid, Christoph Schmetzer, Helga Maria Int J Mol Sci Article Dendritic cells (DC) and leukaemia derived DC (DC(leu)) 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(leu)-generating protocols. With respect to future clinical applications though, DC/DC(leu)-generating protocols specifically designed for application in a whole-blood-(WB)-environment must be established. Therefore, we developed ten new DC/DC(leu)-generating protocols (kits; Kit-A/-C/-D/-E/-F/-G/-H/-I/-K/-M) for the generation of DC/DC(leu) from leukaemic WB, containing calcium-ionophore, granulocyte-macrophage-colony-stimulating-factor (GM-CSF), tumour-necrosis-factor-alpha, prostaglandin-E(1) (PGE(1)), prostaglandin-E(2) (PGE(2)) and/or picibanil (OK-432). All protocols were evaluated regarding their performance in generating DC/DC(leu) using refined classification and/or ranking systems; DC/DC(leu) 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(leu) from leukaemic WB. Through refined classification and ranking systems, we were able to select Kit-I (GM-CSF + OK-432), -K (GM-CSF + PGE(2)) and -M (GM-CSF + PGE(1)) as the most efficient kits in generating (mature) DC/DC(leu), 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(leu)-based anti-leukaemic immunity in a WB-environment in vitro constitutes an important and directive step for translating DC/DC(leu)-based immunotherapy of AML into clinical application. MDPI 2022-07-28 /pmc/articles/PMC9368668/ /pubmed/35955486 http://dx.doi.org/10.3390/ijms23158333 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schwepcke, Christoph
Klauer, Lara Kristina
Deen, Diana
Amberger, Daniel Christoph
Fischer, Zuzana
Doraneh-Gard, Fatemeh
Gunsilius, Carina
Hirn-Lopez, Annika
Kroell, Tanja
Tischer, Johanna
Weinmann, Melanie
Werner, Jan-Ole
Rank, Andreas
Schmid, Christoph
Schmetzer, Helga Maria
Generation of Leukaemia-Derived Dendritic Cells (DC(leu)) to Improve Anti-Leukaemic Activity in AML: Selection of the Most Efficient Response Modifier Combinations
title Generation of Leukaemia-Derived Dendritic Cells (DC(leu)) to Improve Anti-Leukaemic Activity in AML: Selection of the Most Efficient Response Modifier Combinations
title_full Generation of Leukaemia-Derived Dendritic Cells (DC(leu)) to Improve Anti-Leukaemic Activity in AML: Selection of the Most Efficient Response Modifier Combinations
title_fullStr Generation of Leukaemia-Derived Dendritic Cells (DC(leu)) to Improve Anti-Leukaemic Activity in AML: Selection of the Most Efficient Response Modifier Combinations
title_full_unstemmed Generation of Leukaemia-Derived Dendritic Cells (DC(leu)) to Improve Anti-Leukaemic Activity in AML: Selection of the Most Efficient Response Modifier Combinations
title_short Generation of Leukaemia-Derived Dendritic Cells (DC(leu)) to Improve Anti-Leukaemic Activity in AML: Selection of the Most Efficient Response Modifier Combinations
title_sort generation of leukaemia-derived dendritic cells (dc(leu)) to improve anti-leukaemic activity in aml: selection of the most efficient response modifier combinations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368668/
https://www.ncbi.nlm.nih.gov/pubmed/35955486
http://dx.doi.org/10.3390/ijms23158333
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