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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/15/8333 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Christoph Schwepcke |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T10:08:36Z |
| format | Article |
| id | doaj.art-6c3bc76e842e44e288be41db05f2287c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T10:08:36Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6c3bc76e842e44e288be41db05f2287c2023-12-01T22:57:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012315833310.3390/ijms23158333Generation of Leukaemia-Derived Dendritic Cells (DC<sub>leu</sub>) to Improve Anti-Leukaemic Activity in AML: Selection of the Most Efficient Response Modifier CombinationsChristoph Schwepcke0Lara Kristina Klauer1Diana Deen2Daniel Christoph Amberger3Zuzana Fischer4Fatemeh Doraneh-Gard5Carina Gunsilius6Annika Hirn-Lopez7Tanja Kroell8Johanna Tischer9Melanie Weinmann10Jan-Ole Werner11Andreas Rank12Christoph Schmid13Helga Maria Schmetzer14Department of Medicine III, University Hospital of Munich, 81377 Munich, GermanyDepartment of Medicine III, University Hospital of Munich, 81377 Munich, GermanyDepartment of Medicine III, University Hospital of Munich, 81377 Munich, GermanyDepartment of Medicine III, University Hospital of Munich, 81377 Munich, GermanyDepartment of Medicine III, University Hospital of Munich, 81377 Munich, GermanyDepartment of Medicine III, University Hospital of Munich, 81377 Munich, GermanyDepartment of Medicine III, University Hospital of Munich, 81377 Munich, GermanyDepartment of Medicine III, University Hospital of Munich, 81377 Munich, GermanyDepartment of Medicine III, University Hospital of Munich, 81377 Munich, GermanyDepartment of Medicine III, University Hospital of Munich, 81377 Munich, GermanyDepartment of Medicine III, University Hospital of Munich, 81377 Munich, GermanyDepartment of Haematology and Oncology, University Hospital of Tuebingen, 72076 Tuebingen, GermanyDepartment of Haematology and Oncology, University Hospital of Augsburg, 86156 Augsburg, GermanyDepartment of Haematology and Oncology, University Hospital of Augsburg, 86156 Augsburg, GermanyDepartment of Medicine III, University Hospital of Munich, 81377 Munich, GermanyDendritic 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.https://www.mdpi.com/1422-0067/23/15/8333leukaemia derived DCacute myeloid leukaemiaanti-leukaemic functionality |
| spellingShingle | 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 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 International Journal of Molecular Sciences leukaemia derived DC acute myeloid leukaemia anti-leukaemic functionality |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | leukaemia derived DC acute myeloid leukaemia anti-leukaemic functionality |
| url | https://www.mdpi.com/1422-0067/23/15/8333 |
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