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Immune modulation of AML-blasts in therapy-refractory AML-patient in vivo with clinically approved response modifiers improves clinical status, blood cell regeneration and gives rise to leukemia specific adaptive and innate immune reactive cells

      Background: Three kits of immune-modulatory compounds, (GM-CSF, combined either with Picibanil (Kit “I”), Prostaglandine (PG) E2 (Kit “K”) or PGE1 (Kit “M”)) were identified to effectively convert myeloid blasts into dendritic cells of leukemic origin (DCleu). After stimulation with DCleu, antileukemic T-cells can be generated ex vivo (patent 102014014993). The compounds are approved for clinical use and are therefore attractive tools for immunotherapy in myeloid leukemia. For in vivo testing, a rodent model with AML-diseased rats was used: Three rats each were treated with “I”, “K” or “M”. Untreated animals with AML and healthy rats served as controls. A significant reduction of blasts was seen with “M” (p=0.03/0.0001 in spleen/PB) and “I”, but not “K”. Successful treatment correlated with an increase of CD62L+ cells, most likely representing Tmem-cells, (p=0.07) and a reduction of CD4+Treg (p=0.037). Based on these data, an individual salvage treatment was performed in a patient with refractory AML.
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