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Effects of TLR agonists on maturation and function of 3-day dendritic cells from AML patients in complete remission.
J. Transl. Med. 9:151 (2011)
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. 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. 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. 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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
acute myeloid-leukemia; wt1 peptide vaccination; t-cells; immunity; induction; responses; cancer; interleukin-12; activation; generation
ISSN (print) / ISBN
1479-5876
e-ISSN
1479-5876
Quellenangaben
Volume: 9,
Issue: 1,
Article Number: 151
Publisher
BioMed Central
Non-patent literature
Publications
Reviewing status
Peer reviewed