P07.01 The potential role of extracellular vesicle-derived small RNAS in AML research as non-invasive biomarker

• Published in: Journal for immunotherapy of cancer Vol. 10; no. Suppl 1; pp. A24 - A25
• Main Authors: Li, L, Mussack, V, Görgens, A, Pepeldjiyska, E, Hartz, AS, Aslan, H, Rackl, E, Rank, A, Schmohl, J, Pfaffl, MW, Schmetzer, H
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 21-09-2022; BMJ Publishing Group LTD
• Subjects: Biomarkers; Extracellular vesicles; Immunotherapy; Leukemia; Poster Presentations
• ISSN: 2051-1426
• DOI: 10.1136/jitc-2022-ITOC9.45

BackgroundAntileukemic responses of immune reactive cells in AML-patients need to be improved. Combinations of blast-modulatory kitM (GM-CSF+PGE1) (vs control) convert myeloid blasts into dendritic cells of leukemic origin (DCleu), that effectively activate immune-cells against leukemic blasts. DC-derived EVs express molecules and carry nucleic acids (eg. miRNA) with immune regulatory functions.Materials and Methods1) DC/DCleu-generation of blast containing AML patients‘ (n=5) and of healthy volunteers(n=5) whole blood (WB) with kit M; 2) T-cell enriched mixed lymphocyte culture (MLC) with kit- vs un-treated WB; 3) antileukemic functional assays; 4) Sequencing of EV-derived miRNA from culture supernatants; 5) Qualitative/quantitative characterization of (leukemia/healthy) supernatant derived EVs and EV derived miRNAs as biomarkers.Results1) kitM increased significantly frequencies of (mature) DC/DCleu compared to untreated WB without induction of blasts’ proliferation. 2) kitM treated vs untreated WB increased significantly activated (leukemia-specific) cells of the adaptive and innate immune system after T cell-enriched MLC. 3a) EVs were qualitatively and quantitatively different in DC/MLC culture supernatants compared control as well as 3b) in kitM treated vs untreated healthy and AML samples. 3c) Different EV derived miRNAs were up- or downregulated in DC/MLC culture supernatants.ConclusionsThese findings contribute to understand the unique/functional role of (leukemic derived) DCs to improve antileukemic immune responses, with respect to the role of EVs/EV derived miRNA and to potentially deduce new EV derived biomarkers.Disclosure Information L. Li: None. V. Mussack: None. A. Görgens: None. E. Pepeldjiyska: None. A.S. Hartz: None. H. Aslan: None. E. Rackl: None. A. Rank: None. J. Schmohl: None. M.W. Pfaffl: None. H. Schmetzer: None.