In Vivo Induction of Leukemia-Specific Adaptive and Innate Immune Cells by Treatment of AML-Diseased Rats and Therapy-Refractory AML Patients with Blast Modulating Response Modifiers.

There is a high medical need to develop new strategies for the treatment of patients with acute myeloid leukemia (AML) refractory to conventional therapy. In vitro, the combinations of the blast-modulatory response modifiers GM-CSF + Prostaglandin E1, (summarized as Kit M) have been shown to convert myeloid leukemic blasts into antigen-presenting dendritic cells of leukemic origin (DC) that were able to (re-)activate the innate and adaptive immune system, direct it specifically against leukemic blasts, and induce memory cells. This study aimed to investigate the immune modulatory capacity and antileukemic efficacy of Kit M in vivo.

Dendritic/antigen presenting cell mediated provision of T-cell receptor gamma delta (TCRγδ) expressing cells contributes to improving antileukemic reactions ex vivo.

T-cell receptor gamma delta (TCRγδ) expressing T-cells are known to mediate an MHC-independent immune response and could therefore qualify for immune therapies. We examined the influence of dendritic cells(DC)/antigen presenting cell (APC) generated from blast-containing whole blood (WB) samples from AML and MDS patients on the provision of (leukemia-specific) TCRγδ expressing T-cells after mixed lymphocyte culture (MLC). Kit-M (granulocyte-macrophage colony-stimulating factor (GM-CSF) + prostaglandin E1 (PGE1)) or Kit-I (GM-CSF + Picibanil) were used to generate leukemia derived APC/DC (DC)from WB, which were subsequently used to stimulate T-cell enriched MLC.

Anti-Leukemic Effects Induced by Dendritic Cells of Leukemic Origin from Leukemic Blood Samples Are Comparable under Hypoxic vs. Normoxic Conditions.

Hypoxia can modulate the immune system by affecting the function and activity of immune cells, potentially leading to altered immune responses. This study investigated the generation of leukemia-derived dendritic cells (DC from leukemic blasts and their impact on immune cell activation under hypoxic (5-10% O) compared to normoxic (21% O) conditions using various immunomodulatory Kits. The results revealed that DC/DC-generation was similar under hypoxic and normoxic conditions, with no significant differences observed in frequencies of generated DC/DC.

Effective and Successful Quantification of Leukemia-Specific Immune Cells in AML Patients' Blood or Culture, Focusing on Intracellular Cytokine and Degranulation Assays.

Novel (immune) therapies are needed to stabilize remissions or the disease in AML. Leukemia derived dendritic cells (DCleu) can be generated ex vivo from AML patients' blasts in whole blood using approved drugs (GM-CSF and PGE-1 (Kit M)). After T cell enriched, mixed lymphocyte culture (MLC) with Kit M pretreated (vs.

Granulocyte-Macrophage-Colony-Stimulating-Factor Combined with Prostaglandin E1 Create Dendritic Cells of Leukemic Origin from AML Patients' Whole Blood and Whole Bone Marrow That Mediate Antileukemic Processes after Mixed Lymphocyte Culture.

Although several (chemotherapeutic) protocols to treat acute myeloid leukemia (AML) are available, high rates of relapses in successfully treated patients occur. Strategies to stabilize remissions are greatly needed. The combination of the (clinically approved) immune-modulatory compounds Granulocyte-Macrophage-Colony-Stimulating-Factor (GM-CSF) and Prostaglandine E1 (PGE-1) (Kit-M) converts myeloid blasts into dendritic cells of leukemic origin (DC).