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- Title
Effects of TLR agonists on maturation and function of 3-day dendritic cells from AML patients in complete remission.
- Authors
Beck, Barbara; Dörfel, Daniela; Lichtenegger, Felix S; Geiger, Christiane; Lindner, Lysann; Merk, Martina; Schendel, Dolores J; Subklewe, Marion
- Abstract
<bold>Background: </bold>Active dendritic cell (DC) immunization protocols are rapidly gaining interest as therapeutic options in patients with acute myeloid leukemia (AML). Here we present for the first time a GMP-compliant 3-day protocol for generation of monocyte-derived DCs using different synthetic Toll-like receptor (TLR) agonists in intensively pretreated patients with AML.<bold>Methods: </bold>Four different maturation cocktails were compared for their impact on cell recovery, phenotype, cytokine secretion, migration, and lymphocyte activation in 20 AML patients and 25 healthy controls.<bold>Results: </bold>Maturation cocktails containing the TLR7/8 agonists R848 or CL075, with and without the addition of the TLR3 agonist poly(I:C), induced DCs that had a positive costimulatory profile, secreted high levels of IL-12(p70), showed chemotaxis to CCR7 ligands, had the ability to activate NK cells, and efficiently stimulated antigen-specific CD8+ T cells.<bold>Conclusions: </bold>Our results demonstrate that this approach translates into biologically improved DCs, not only in healthy controls but also in AML patients. This data supports the clinical application of TLR-matured DCs in patients with AML for activation of innate and adaptive immune responses.
- Subjects
CELL differentiation; DENDRITIC cells; BIOMARKERS; CYTOKINES; INTERLEUKINS; PROTEINS; TIME; CELL physiology; KILLER cells; IMMUNOLOGY technique; CELL receptors; TOLL-like receptor agonists; CELLS; PHOSPHOPROTEINS; T cells; DISEASE remission
- Publication
Journal of Translational Medicine, 2011, Vol 9, Issue 1, p151
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/1479-5876-9-151