title: Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme.
abstract: OBJECTIVE
  The object of this study was to investigate the safety and clinical responses of immunotherapy targeting the WT1 (Wilms tumor 1) gene product in patients with recurrent glioblastoma multiforme (GBM).
  
  
  METHODS
  Twenty-one patients with WT1/HLA-A*2402-positive recurrent GBM were included in a Phase II clinical study of WT1 vaccine therapy. In all patients, the tumors were resistant to standard therapy. Patients received intra-dermal injections of an HLA-A*2402-restricted, modified 9-mer WT1 peptide every week for 12 weeks. Tumor size, which was obtained by measuring the contrast-enhanced area on magnetic resonance images, was determined every 4 weeks. The responses were analyzed according to Response Evaluation Criteria in Solid Tumors (RECIST) 12 weeks after the initial vaccination. Patients who achieved an effective response continued to be vaccinated until tumor progression occurred. Progression-free survival and overall survival after initial WT1 treatment were estimated.
  
  
  RESULTS
  The protocol was well tolerated; only local erythema occurred at the WT1 vaccine injection site. The clinical responses were as follows: partial response in 2 patients, stable disease in 10 patients, and progressive disease in 9 patients. No patient had a complete response. The overall response rate (cases with complete or partial response) was 9.5%, and the disease control rate (cases with complete or partial response as well as those in which disease was stable) was 57.1%. The median progression-free survival (PFS) period was 20.0 weeks, and the 6-month (26-week) PFS rate was 33.3%.
  
  
  CONCLUSIONS
  Although a small uncontrolled nonrandomized trial, this study showed that WT1 vaccine therapy for patients with WT1/HLA-A*2402-positive recurrent GBM was safe and produced a clinical response. Based on these results, further clinical studies of WT1 vaccine therapy in patients with malignant glioma are warranted.
authors.affiliation: Department of Neurosurgery, Nagoya University, Nagoya, Japan. sizumoto@nsurg.med.osaka-u.ac.jp
authors.forename: Shuichi
authors.initials: S
authors.lastname: Izumoto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Hashiba
authors.forename: Naoki
authors.initials: N
authors.lastname: Kagawa
authors.forename: Naoya
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Motohiko
authors.initials: M
authors.lastname: Maruno
authors.forename: Olga A
authors.initials: OA
authors.lastname: Elisseeva
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shirakata
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Nishida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohno
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
authors.forename: Jun
authors.initials: J
authors.lastname: Hatazawa
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Nakatsuka
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Aozasa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoshimine
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018797:Cell Cycle Proteins; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000276:immunology*; D000072260:RNA Splicing Factors; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; C419554:WTAP protein, human