title: Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma.
abstract: BACKGROUND
  We previously demonstrated that dendritic cell-based immunotherapy induced protective antitumor immunity with a prolonged survival rate in mice. However, the clinical relevance is still in question. To examine this, we designed a clinical trial using chemotherapy followed by antigen-pulsed dendritic cell vaccination in mesothelioma patients.
  
  
  OBJECTIVE
  The aim of this study was to assess the safety and immunological response induced by the administration of tumor lysate-pulsed dendritic cells in patients with mesothelioma.
  
  
  METHODS
  Ten patients with malignant pleural mesothelioma received three vaccinations of clinical-grade autologous dendritic cells intradermally and intravenously at 2-week intervals after chemotherapy. Each vaccine was composed of 50 x 10(6) mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin (KLH) as surrogate marker. Delayed-type hypersensitivity activity to tumor antigens and KLH was assessed, both in vivo and in vitro. Peripheral blood mononuclear cells during the treatment were analyzed for immunological responses.
  
  
  RESULTS
  Administration of dendritic cells pulsed with autologous tumor lysate in patients with mesothelioma was safe with moderate fever as the only side effect. There were no grade 3 or 4 toxicities associated with the vaccines or any evidence of autoimmunity. Local accumulations of infiltrating T cells were found at the site of vaccination. The vaccinations induced distinct immunological responses to KLH, both in vitro and in vivo. Importantly, after three vaccinations, cytotoxic activity against autologous tumor cells was detected in a subgroup of patients.
  
  
  CONCLUSIONS
  This study demonstrated that autologous tumor lysate-pulsed dendritic cell-based therapy is feasible, well-tolerated, and capable of inducing immunological response to tumor cells in mesothelioma patients. Clinical trial registered with www.clinicaltrials.gov (NCT00280982).
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Hegmans
authors.forename: Joris D
authors.initials: JD
authors.lastname: Veltman
authors.forename: Margaretha E
authors.initials: ME
authors.lastname: Lambers
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
authors.forename: Henk C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.forename: Joachim G
authors.initials: JG
authors.lastname: Aerts
mesh_terms: D000368:Aged; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005240:Feasibility Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008654:Mesothelioma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000276:immunology / Q000628:therapy*