粒细胞-巨噬细胞集落刺激因子联合前列腺素 E1 从 AML 患者全血和全骨髓中生成白血病来源的树突状细胞，在混合淋巴细胞培养后介导抗白血病过程

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 leu ). After stimulation with DC leu ex vivo, leukemia-specific antileukemic immune cells are activated.

Therefore, Kit-M treatment may be an attractive immunotherapeutic tool to treat patients with myeloid leukemia. Kit-M-mediated antileukemic effects on whole bone marrow (WBM) were evaluated and compared to whole blood (WB) to evaluate the potential effects of Kit-M on both compartments. WB and WBM samples from 17 AML patients at first diagnosis, in persisting disease and at relapse after allogeneic stem cell transplantation (SCT) were treated in parallel with Kit-M to generate DC/DC leu . Untreated samples served as controls. After a mixed lymphocyte culture enriched with patients' T cells (MLC), the leukemia-specific antileukemic effects were assessed through the degranulation- (CD107a + T cells), the intracellular IFNγ production- and the cytotoxicity fluorolysis assay. Quantification of cell subtypes was performed via flow cytometry. In both WB and WBM significantly higher frequencies of (mature) DC leu were generated without induction of blast proliferation in Kit-M-treated samples compared to control. After MLC with Kit-M-treated vs.

not pretreated WB or WBM, frequencies of (leukemia-specific) immunoreactive cells (e. g. , non-naive, effector-, memory-, CD3 + β7 + T cells, NK- cells) were (significantly) increased, whereas leukemia-specific regulatory T cells (T reg , CD152 + T cells) were (significantly) decreased. The cytotoxicity fluorolysis assay showed a significantly improved blast lysis in Kit-M-treated WB and WBM compared to control. A parallel comparison of WB and WBM samples revealed no significant differences in frequencies of DC leu , (leukemia-specific) immunoreactive cells and achieved antileukemic processes.

Kit-M was shown to have comparable effects on WB and WBM samples regarding the generation of DC leu and activation of (antileukemic) immune cells after MLC. This was true for samples before or after SCT. In summary, a potential Kit-M in vivo treatment could lead to antileukemic effects in WB as well as WBM in vivo and to stabilization of the disease or remission in patients before or after SCT. A clinical trial is currently being planned.