title: Feasibility of Cancer Immunotherapy with WT1 Peptide Vaccination for Solid and Hematological Malignancies in Children.
abstract: BACKGROUND
  Advances in cancer immunotherapy in the pediatric field are needed in order to improve the prognosis of children with malignancies. We conducted a prospective phase I/II study of WT1 peptide vaccination for children with relapsed or refractory malignancies.
  
  
  METHODS
  The main eligibility criteria were affected tissues or leukemic cells expressing the WT1 gene, and patients (and donors for allogeneic hematopoietic stem cell transplantation) having HLA-A*24:02. Vaccination using the WT1 peptide (CYTWNQMNL), which was modified for higher affinity to this HLA-type molecule with the adjuvant Montanide ISA51, was performed weekly 12 times.
  
  
  RESULTS
  Twenty-six patients were enrolled and 13 (50.0%) completed the vaccination 12 times. Evidence for the induction of WT1-specific cytotoxic T-lymphocyte (CTL) responses without severe systemic side effects was obtained. Two out of 12 patients with bulky disease exhibited a transient clinical effect (one mixed response and one stable disease), three out of six patients with minimal residual disease achieved transient molecular remission, and five out of eight patients without a detectable level of the molecular marker, but with a high risk of relapse, had the best outcome of long-term continuous complete remission.
  
  
  CONCLUSIONS
  WT1 vaccination is a safe immunotherapy and induced WT1-specific CTL responses in children; however, as a single agent, vaccination only provided patients in remission, but with a high risk of relapse, with "long-term benefits" in the context of its use for relapse prevention. WT1 peptide-based treatments in combination with other modalities, such as anti-tumor drugs or immunomodulating agents, need to be planned.
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Sawada
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kondo
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Yamada-Nakata
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishihara
authors.affiliation: Department of Pathology and Clinical Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.|Department of Diagnostic Pathology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kuwae
authors.affiliation: Department of Radiology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Pharmacy, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ammori
authors.affiliation: Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.affiliation: Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Koyama-Sato
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.|Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan.|Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yasui
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Keisei
authors.initials: K
authors.lastname: Kawa
mesh_terms: D000276:Adjuvants, Immunologic; D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D009829:Oleic Acids / Q000008:administration & dosage; D010455:Peptides / Q000276:immunology / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D025721:WT1 Proteins / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D009829:Oleic Acids; D010455:Peptides; D025721:WT1 Proteins; C583751:WT1 protein, human; C477385:montanide ISA 51; D008353:Mannitol
keywords: WT1 vaccine; immunotherapy; leukemia; pediatrics; solid tumor