title: Dendritic cell-based immunotherapy targeting Wilms' tumor 1 in patients with recurrent malignant glioma.
abstract: OBJECTIVE
  Dendritic cell (DC)-based vaccination is considered a potentially effective therapy against advanced cancer. The authors conducted a Phase I study to investigate the safety and immunomonitoring of Wilms' tumor 1 (WT1)-pulsed DC vaccination therapy for patients with relapsed malignant glioma.
  
  
  METHODS
  WT1-pulsed and/or autologous tumor lysate-pulsed DC vaccination therapy was performed in patients with relapsed malignant gliomas. Approximately 1 × 10(7) to 2 × 10(7) pulsed DCs loaded with WT1 peptide antigen and/or tumor lysate were intradermally injected into the axillary areas with OK-432, a streptococcal preparation, at 2-week intervals for at least 5-7 sessions (1 course) during an individual chemotherapy regimen.
  
  
  RESULTS
  Ten patients (3 men, 7 women; age range 24-64 years [median 39 years]) with the following tumors were enrolled: glioblastoma (6), anaplastic astrocytoma (2), anaplastic oligoastrocytoma (1), and anaplastic oligodendroglioma (1). Modified WT1 peptide-pulsed DC vaccine was administered to 7 patients, tumor lysate-pulsed DC vaccine to 2 patients, and both tumor lysate-pulsed and WT1-pulsed DC vaccine to 1 patient. The clinical response was stable disease in 5 patients with WT1-pulsed DC vaccination. In 2 of 5 patients with stable disease, neurological findings improved, and MR images showed tumor shrinkage. No serious adverse events occurred except Grade 1-2 erythema at the injection sites. WT1 tetramer analysis detected WT1-reactive cytotoxic T cells after vaccination in patients treated with WT1-pulsed therapy. Positivity for skin reaction at the injection sites was 80% (8 of 10 patients) after the first session, and positivity remained for these 8 patients after the final session.
  
  
  CONCLUSIONS
  This study of WT1-pulsed DC vaccination therapy demonstrated safety, immunogenicity, and feasibility in the management of relapsed malignant gliomas.
authors.affiliation: Department of Neurosurgery, Shinshu University School of Medicine;|Department of Neurosurgery, National Hospital Organization, Shinshu Ueda Medical Center, Ueda, Nagano, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Center for Advanced Cellular Therapy, Shinshu University Hospital, Matsumoto;
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Shimodaira
authors.affiliation: Dendritic Cell Vaccination Therapy Center.
authors.forename: Shinya
authors.initials: S
authors.lastname: Maejima
authors.affiliation: Dendritic Cell Vaccination Therapy Center.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Udagawa
authors.affiliation: Department of Laboratory, Shinshu University Hospital, Matsumoto;
authors.forename: Kenji
authors.initials: K
authors.lastname: Sano
authors.affiliation: Center for Advanced Cellular Therapy, Shinshu University Hospital, Matsumoto;
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Higuchi
authors.affiliation: Center for Advanced Cellular Therapy, Shinshu University Hospital, Matsumoto;
authors.forename: Terutsugu
authors.initials: T
authors.lastname: Koya
authors.affiliation: Department of Oral Pathology.
authors.forename: Takanaga
authors.initials: T
authors.lastname: Ochiai
authors.affiliation: Institute for Oral Science, and.
authors.forename: Masanori
authors.initials: M
authors.lastname: Koide
authors.affiliation: Department of Biochemistry, Matsumoto Dental University Hospital, Shiojiri;
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Uehara
authors.affiliation: Department of Biochemistry, Matsumoto Dental University Hospital, Shiojiri;
authors.forename: Midori
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Functional Diagnostic Science, Graduate School of Medicine, Osaka University, Osaka;
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
authors.affiliation: R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka;
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yonemitsu
authors.affiliation: Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Minato-ku, Tokyo; and.
authors.forename: Masato
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Department of Neurosurgery, Shinshu University School of Medicine;
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hongo
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy; D019496:Cancer Vaccines; D003713:Dendritic Cells; D005260:Female; D005910:Glioma / Q000473:pathology / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007680:Kidney Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy; D009396:Wilms Tumor / Q000628:therapy*; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines
keywords: CTL = cytotoxic T lymphocyte; DC = dendritic cell; HLA = human leukocyte antigen; IL = interleukin; KPS = Karnofsky Performance Scale; Ke = kiloequivalent; MST = median overall survival time; PD = progressive disease; PR = partial response; RECIST = Response Evaluation Criteria in Solid Tumors; SD = stable disease; TAA = tumor-associated antigen; WT1; WT1 = Wilms’ tumor 1; dendritic cell; immunotherapy; oncology; relapsed malignant glioma