Lara Kristina Klauer, Hazal Aslan Rejeski, Selda Ugur, Elias Rackl, Joudi Abdulmajid, Zuzanna Fischer, Elena Pepeldjiyska, Annalena Frischhut, Nicolas Schmieder, Antje Völker, Andreas Rank, Christoph Schmid, Jörg Schmohl, Daniel Christoph Amberger, Helga Maria Schmetzer
- New therapies are highly needed to stabilize remission in patients with acute myeloid leukemia (AML). This study investigates the value of dendritic cells derived from leukemic blasts (DCleu) to enhance anti-leukemic immunity after T-cell-enriched mixed lymphocyte cultures (MLCs). We correlated induced anti-leukemic activity with patient data, including biological, clinical and prognostic factors. Additionally, we correlated the frequencies of DC/DCleu and leukemic-specific T cells with the achieved anti-leukemic activity after MLC. We show that mature DC/DCleu can be generated using the immunomodulating Kit-M, which contains granulocyte–macrophage colony-stimulating-factor (GM-CSF) and prostaglandin E1 (PGE1), without inducing blast proliferation from leukemic whole blood (WB) samples. Activated leukemia-specific immune and memory cells increased after MLC with Kit-M-pretreated WB, leading to improved blast lysis. Enhanced anti-leukemic activity positively correlated with theNew therapies are highly needed to stabilize remission in patients with acute myeloid leukemia (AML). This study investigates the value of dendritic cells derived from leukemic blasts (DCleu) to enhance anti-leukemic immunity after T-cell-enriched mixed lymphocyte cultures (MLCs). We correlated induced anti-leukemic activity with patient data, including biological, clinical and prognostic factors. Additionally, we correlated the frequencies of DC/DCleu and leukemic-specific T cells with the achieved anti-leukemic activity after MLC. We show that mature DC/DCleu can be generated using the immunomodulating Kit-M, which contains granulocyte–macrophage colony-stimulating-factor (GM-CSF) and prostaglandin E1 (PGE1), without inducing blast proliferation from leukemic whole blood (WB) samples. Activated leukemia-specific immune and memory cells increased after MLC with Kit-M-pretreated WB, leading to improved blast lysis. Enhanced anti-leukemic activity positively correlated with the frequencies of generated DC/DCleu, proliferating leukemic-specific T cells and memory T cells, but not with leukemic blast counts, hemoglobin levels or platelet counts at diagnosis. No correlation was found between improved blast lysis and patients’ prognostic data, including age, gender, ELN risk groups, disease stage and response to induction chemotherapy. These findings underscore the potential of DC/DCleu to evoke robust immune responses and potential immunological memory against AML. Overall, this innovative approach could pave the way for the development of improved immunotherapeutic strategies that function in vivo.…
