title: Immunotherapy of murine malignant mesothelioma using tumor lysate-pulsed dendritic cells.
abstract: BACKGROUND
  Exploiting the immunostimulatory capacities of dendritic cells holds great promise for cancer immunotherapy. Currently, dendritic cell-based immunotherapy is evaluated clinically in a number of malignancies, including melanoma and urogenital and lung cancer, showing variable but promising results.
  
  
  OBJECTIVE
  To evaluate if pulsed dendritic cells induce protective immunity against malignant mesothelioma in a mouse model.
  
  
  METHODS
  Malignant mesothelioma was induced in mice by intraperitoneal injection of the AB1 mesothelioma cell line, leading to death within 28 days. For immunotherapy, dendritic cells were pulsed overnight either with AB1 tumor cell line lysate, AB1-derived exosomes, or ex vivo AB1 tumor lysate, and injected either before (Days -14 and -7) at the day of (Day 0) or after (Days +1 and +8) tumor implantation.
  
  
  RESULTS
  Mice receiving tumor lysate-pulsed dendritic cells before tumor implantation demonstrated protective antitumor immunity with prolonged survival (> 3 months) and even resisted secondary tumor challenge. Tumor protection was associated with strong tumor-specific cytotoxic T-lymphocyte responses. Adoptive transfer of splenocytes or purified CD8+ T lymphocytes transferred tumor protection to unimmunized mice in vivo. When given after tumor implantation in a therapeutic setting, pulsed dendritic cells prevented mesothelioma outgrowth. With higher tumor load and delayed administration after tumor implantation, dendritic cells were no longer effective.
  
  
  CONCLUSIONS
  We demonstrate in this murine model that immunotherapy using pulsed dendritic cells may emerge as a powerful tool to control mesothelioma outgrowth. In the future, immunotherapy using dendritic cells could be used as adjuvant to control local recurrence after multimodality treatment for malignant mesothelioma.
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, H-Ee2253a, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. j.hegmans@erasmusmc.nl
authors.forename: Joost P J J
authors.initials: JP
authors.lastname: Hegmans
authors.forename: Annabrita
authors.initials: A
authors.lastname: Hemmes
authors.forename: Joachim G
authors.initials: JG
authors.lastname: Aerts
authors.forename: Henk C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008654:Mesothelioma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines