Functional and Immunological Monitoring of Immune-Reactive and Anti-Leukemic Cells (T, NK, CIK, B-Cells) arising in WB from AML, ALL, or CLL Patients under Treatment with Several Immunomodulatory Approaches

Author(s): Xiaojia Feng, Marianne Unterfrauner, Sophia Bohlscheid, Philipp Anand, Lin Li, Hazal Aslan Rejeski, Anne Hartz, Tobias Baudrexler, Joudi Abdulmajid, Anwesha Sinha, Peter Bojko, Doris Kra?mer, Jörg Schmohl, Christoph Schmid, Giuliano Filippini Vela?zquez and Helga Schmetzer

New treatment strategies for acute myeloid leukemia (AML)/ acute lymphocytic leukemia (ALL)/chronic lymphocytic leukemia (CLL) patients are under development. Myeloid/Lymphoid leukemic cells (AML, ALL) can be differentiated into leukemia-derived dendritic cells (DCleu), potentially presenting the entire leukemic antigen repertoire without knowledge of distinct leukemia antigens, and are regarded as a promising candidate for a vaccination strategy. We investigated the effectiveness of three DC/DCleu-generating ‘Kits’, containing Interleukin-4 (IL-4) and CD40 Ligand (CD40L) (termed “Kit-1” ), containing Granulocyte-Macrophage-Colony-Stimulating-Factor (GM-CSF), Interleukin-4 (IL-4) and Tumor Necrosis Factor Alpha (TNFα) (termed “Kit-2” ), containing Granulocyte-Macrophage-colony-Stimulating-factor (GM-CSF) and Prostaglandin-E1 (PGE-1) (termed “Kit-M”), to enhance anti-leukemic effector/memory immune cells after T-cell-enriched mixed lymphocyte cultures (MLC), as induced by DC/DCleu generated ex vivo from AML, ALL, CLL patients` and Healthy donors` whole blood (WB). Kit-M (vs. Kit-1 and Kit-2) induced the strongest antileukemic effects in AML patients` WB. Mature DC/DCs were most effectively generated using Kit-1 (vs. Kit-2 and Kit-M) without inducing blast proliferation in ALL and CLL patients' WB and increased leukemia-specific immune and memory cells after MLC, leading to improved blast lysis. Overall, these findings underscore the potential of Kit-(especially Kit-M) induced DC/DCleu to evoke robust antileukemic immune responses and immunological memory against AML/ALL.