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Open Access 01-12-2011 | Research

Effects of TLR agonists on maturation and function of 3-day dendritic cells from AML patients in complete remission

Authors: Barbara Beck, Daniela Dörfel, Felix S Lichtenegger, Christiane Geiger, Lysann Lindner, Martina Merk, Dolores J Schendel, Marion Subklewe

Published in: Journal of Translational Medicine | Issue 1/2011

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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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: Barbara Beck
Daniela Dörfel
Felix S Lichtenegger
Christiane Geiger
Lysann Lindner
Martina Merk
Dolores J Schendel
Marion Subklewe
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2011
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/1479-5876-9-151

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Effects of TLR agonists on maturation and function of 3-day dendritic cells from AML patients in complete remission

Abstract

Background

Methods

Results

Conclusions

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Abstract

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Conclusions

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