title: Phenotypic and functional characterization of clinical grade dendritic cells generated from patients with advanced breast cancer for therapeutic vaccination.
abstract: Dendritic cells (DC) are promising candidates for cancer immunotherapy. However, it is not known whether in vitro-generated monocyte-derived DC from cancer patients are altered compared with DC from healthy donors. In a clinical phase I/II study, monocyte-derived DC were generated in vitro utilizing granulocyte macrophage colony-stimulating factor and rh-interleukin-4 (IL-4) and used for cancer immunotherapy. In this study, we tested the effect of various maturation cocktails and performed a comparative evaluation of the DC phenotype and functional characteristics. Polyriboinosinic polyribocytidylic acid (Poly I:C) + tumour necrosis factor-alpha (TNF-alpha) induced significant IL-12 p70 secretion, which was increased after addition of a decoy IL-10 receptor. The lymph node homing chemokine receptor CCR-7 expression was induced by TNF-alpha + IL-1beta + IL-6 + prostaglandin E2 but was not induced by Poly I:C + TNF-alpha. In general, DC from patients had an intermediate maturity phenotype with a significantly higher expression of CD40 and CD54 compared with healthy donors. In vitro analyses showed an unimpaired capacity of the patient-derived DC for antigen-specific (cytomegalovirus, tetanus and keyhole limpet haemocyanin) T-cell stimulation, whereas the allostimulatory capacity of patient-derived DC was significantly decreased. These data suggest that patient-derived DC are more differentiated but are less sensitive to maturation-inducing agents than DC obtained from healthy individuals.
authors.affiliation: Laboratory of Cellular Immunology, Department of Medical Anatomy A, University of Copenhagen, Copenhagen, Denmark. elmpedersen@mai.ku.dk
authors.forename: A E
authors.initials: AE
authors.lastname: Pedersen
authors.forename: M
authors.initials: M
authors.lastname: Thorn
authors.forename: M
authors.initials: M
authors.lastname: Gad
authors.forename: M R
authors.initials: MR
authors.lastname: Walter
authors.forename: H E
authors.initials: HE
authors.lastname: Johnsen
authors.forename: E
authors.initials: E
authors.lastname: Gaarsdal
authors.forename: K
authors.initials: K
authors.lastname: Nikolajsen
authors.forename: S
authors.initials: S
authors.lastname: Buus
authors.forename: M H
authors.initials: MH
authors.lastname: Claesson
authors.forename: I M
authors.initials: IM
authors.lastname: Svane
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology* / Q000628:therapy; D019496:Cancer Vaccines / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003587:Cytomegalovirus / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015232:Dinoprostone / Q000276:immunology / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
chemical_list: C515370:CCR7 protein, human; D019496:Cancer Vaccines; D007375:Interleukin-1; D021122:Protein Subunits; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D013745:Tetanus Toxoid; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D015232:Dinoprostone; D011070:Poly I-C