Generation of leukaemia-derived dendritic cells (DCleu) to improve anti-lukaemic activity in AML

Schwepcke, Christoph (2026): Generation of leukaemia-derived dendritic cells (DCleu) to improve anti-lukaemic activity in AML: selection of the most efficient response modifier combinations. Dissertation, LMU München: Faculty of Medicine

Abstract

Dendritic cells (DC) and leukaemia-derived DC (DCleu) are powerful in stimulating antileukaemic effectivity in acute myeloid leukaemia (AML). They can be generated from mononuclear cells in vitro using standard methods for generating DC/DCleu. However, in the prospect of clinical applications of DCleu in the future, a generation of DC/DCleu in a whole blood-(WB)-environment needs to be developed. We therefore derived ten new protocols of DC/DCleu-generation (Kits; Kit-A/ -C/ -D/ -E/ -F/ -G/ -H/ -I/ -K/ -M), specifically designed for the generation of DC/DCleu in leukaemic WB. These Kits consist of granulocyte-macrophagecolony-stimulating-factor (GM-CSF), tumor-necrosis-factor-alpha (TNFa), calcium-ionophore (Ca), prostaglandine-E1 (PGE1), prostaglandine-E2 (PGE2) and/or picibanil (OK-432). An evaluation of all methods was conducted concerning their capability in generating DC/DCleu by applying a sophisticated ranking and/or classification system; The capability of DC/DCleu to increase anti-leukaemic effectivity was analyzed by utilizing a cytotoxicity fluorolysis assay applied after mixed lymphocyte culture (MLC) using patients´ T-cells and Kit treated WB as stimulator cells. In summary, we could show that the new Kits were able to generate (mature) DC/DCleu from leukaemic WB. By using sophisticated ranking and classification systems, it was possible to choose Kit-I (GM-CSF + OK-432), -K (GM-CSF + PGE2) and -M (GM-CSF + PGE1) as the most proficient Kits in the generation of (mature) DC/DCleu. These generated DC/DCleu were furthermore observed to be capable of stimulating immunoreactive cells in MLC and therefore showed an increased anti-leukaemic cytotoxicity. Demonstrating such a strong potential by Kit-I, -K and -M to mediate anti-leukaemic immunity in a WB-environment through DC/DCleu-generation in vitro, enables further investigations to transfer immunotherapy of AML based on DC/DCleu-generation into a clinical application.

• Item Type: Theses (Dissertation, LMU Munich)
• Subjects: 600 Technology, Medicine; 600 Technology, Medicine > 610 Medical sciences and medicine
• Faculties: Faculty of Medicine
• Language: English
• Date of oral examination: 21. May 2026
• 1. Referee: Schmetzer, Helga
• Signature of the printed copy: 0700/UMD 22847