title: Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical phase I/II trial.
abstract: OBJECTIVE
  To investigate the safety and the immunologic and clinical responses of dendritic cell therapy for patients with recurrent malignant glioma.
  
  
  METHODS
  Twenty-four patients with recurrent malignant glioma (6 grade 3 and 18 grade 4 patients) were evaluated in a phase I/II clinical study of dendritic cell therapy. All patients were resistant to the standard maximum therapy. The patient's peripheral blood dendritic cells were generated with granulocyte macrophage colony-stimulating factor, plus interleukin 4 with or without OK-432, and pulsed with an autologous tumor lysate. Dendritic cells were injected intradermally, or both intratumorally and intradermally every 3 weeks.
  
  
  RESULTS
  The protocols were well tolerated with only local redness and swelling at the injection site in several cases. Clinical responses were as follows: 1 patient with partial response, 3 patients with minor response, 10 patients with stable disease, and 10 patients with progressive disease. The patients whose dendritic cells were matured with OK-432 had longer survival times than the dendritic cells from patients without OK-432 maturation. The patients with both intratumoral and intradermal administrations had a longer survival time than the patients with intradermal administration only. Increased ELISPOT and delayed-type hypersensitivity responses after vaccination could provide good laboratory markers to predict the clinical outcome of patients receiving dendritic cell vaccination. The overall survival of patients with grade 4 glioma was 480 days, which was significantly better than that in the control group.
  
  
  CONCLUSIONS
  This study showed the safety and clinical response of autologous tumor lysate-pulsed dendritic cell therapy for patients with malignant glioma. Dendritic cell therapy is recommended for further clinical studies in malignant glioma patients.
authors.affiliation: Department of Neurosurgery, Brain Research Institute, Niigata University School of Medicine, Niigata University, Niigata, Japan. ryaman@bri-niigata-u.ac.jp
authors.forename: Ryuya
authors.initials: R
authors.lastname: Yamanaka
authors.forename: Junpei
authors.initials: J
authors.lastname: Homma
authors.forename: Naoki
authors.initials: N
authors.lastname: Yajima
authors.forename: Naoto
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Masakazu
authors.initials: M
authors.lastname: Sano
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Abe
authors.forename: Miwako
authors.initials: M
authors.lastname: Narita
authors.forename: Masuhiro
authors.initials: M
authors.lastname: Takahashi
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005910:Glioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007271:Injections, Intradermal; D015552:Injections, Intralesional; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines