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

Abstract

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.