title: Extended Tumor Control after Dendritic Cell Vaccination with Low-Dose Cyclophosphamide as Adjuvant Treatment in Patients with Malignant Pleural Mesothelioma.
abstract: We demonstrated previously that autologous tumor lysate-pulsed dendritic cell-based immunotherapy in patients with malignant pleural mesothelioma is feasible, well-tolerated, and capable of inducing immunologic responses against tumor cells. In our murine model, we found that reduction of regulatory T cells with metronomic cyclophosphamide increased the efficacy of immunotherapy.
  
  
  
  To assess the decrease in number of peripheral blood regulatory T cells during combination therapy of low-dose cyclophosphamide and dendritic cell immunotherapy and determine the induction of immunologic responses with this treatment in patients with mesothelioma.
  
  
  
  Ten patients with malignant pleural mesothelioma received metronomic cyclophosphamide and dendritic cell-based immunotherapy. During the treatment, peripheral blood mononuclear cells were analyzed for regulatory T cells and immunologic responses.
  
  
  
  Administration of dendritic cells pulsed with autologous tumor lysate combined with cyclophosphamide in patients with mesothelioma was safe, the only side effect being moderate fever. Dendritic cell vaccination combined with cyclophosphamide resulted in radiographic disease control in 8 of the 10 patients. Overall survival was promising, with 7 out of 10 patients having a survival of greater than or equal to 24 months and two patients still alive after 50 and 66 months. Low-dose cyclophosphamide reduced the percentage of regulatory T cells of total CD4 cells in peripheral blood from 9.43 (range, 4.34-26.10) to 4.51 (range, 0.27-10.30) after 7 days of cyclophosphamide treatment (P = 0.02).
  
  
  
  Consolidation therapy with autologous tumor lysate-pulsed dendritic cell-based therapy and simultaneously reducing the tumor-induced immune suppression is well-tolerated and shows signs of clinical activity in patients with mesothelioma. Clinical trial registered with www.clinicaltrials.gov (NCT 01241682).
authors.affiliation: 1 Department of Pulmonary Medicine and.
authors.forename: Robin
authors.initials: R
authors.lastname: Cornelissen
authors.affiliation: 1 Department of Pulmonary Medicine and.
authors.forename: Joost P J J
authors.initials: JP
authors.lastname: Hegmans
authors.affiliation: 2 Department of Cardio-Thoracic Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; and.
authors.forename: Alexander P W M
authors.initials: AP
authors.lastname: Maat
authors.affiliation: 1 Department of Pulmonary Medicine and.
authors.forename: Margaretha E H
authors.initials: ME
authors.lastname: Kaijen-Lambers
authors.affiliation: 1 Department of Pulmonary Medicine and.
authors.forename: Koen
authors.initials: K
authors.lastname: Bezemer
authors.affiliation: 1 Department of Pulmonary Medicine and.
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
authors.affiliation: 1 Department of Pulmonary Medicine and.
authors.forename: Henk C
authors.initials: HC
authors.lastname: Hoogsteden
authors.affiliation: 1 Department of Pulmonary Medicine and.|3 Department of Pulmonary Medicine, Amphia Hospital, Breda, the Netherlands.
authors.forename: Joachim G J V
authors.initials: JG
authors.lastname: Aerts
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy / Q000379:methods; D003520:Cyclophosphamide / Q000276:immunology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000276:immunology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010994:Pleura; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*
chemical_list: D000277:Adjuvants, Pharmaceutic; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
keywords: immunosuppression; immunotherapy; pleurectomy/decortication; regulatory T cell; tumor microenvironment