title: Effects of TLR agonists on maturation and function of 3-day dendritic cells from AML patients in complete remission.
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.
authors.affiliation: Department of Internal Medicine III, University of Munich, Campus Grosshadern, Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Beck
authors.forename: Daniela
authors.initials: D
authors.lastname: Dörfel
authors.forename: Felix S
authors.initials: FS
authors.lastname: Lichtenegger
authors.forename: Christiane
authors.initials: C
authors.lastname: Geiger
authors.forename: Lysann
authors.initials: L
authors.lastname: Lindner
authors.forename: Martina
authors.initials: M
authors.lastname: Merk
authors.forename: Dolores J
authors.initials: DJ
authors.lastname: Schendel
authors.forename: Marion
authors.initials: M
authors.lastname: Subklewe
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology; D012074:Remission Induction; D013997:Time Factors; D051193:Toll-Like Receptors / Q000819:agonists* / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D054415:Chemokine CCL19; D010750:Phosphoproteins; D051193:Toll-Like Receptors; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D016753:Interleukin-10; D018664:Interleukin-12