title: Immunotherapy in atypical teratoid-rhabdoid tumors: Data from a survey of the HGG-Immuno Group.
abstract: Atypical rhabdoid/teratoid tumors (AT/RT) are the most common brain tumors in infants and associated with a dismal prognosis. Although intensification of first-line therapy has resulted in improvement of overall survival, novel treatment strategies are needed. Because immunotherapy has resulted in remarkable results in several adult tumor entities, incorporation of immunotherapy into AT/RT treatment offers a novel alternative.
  
  
  
  We retrospectively analyzed data from 7 AT/RT patients from five countries treated within the HGG-Immuno Consortium. Two patients were ≤1 year and 4 patients were ≤2 years of age at diagnosis. All received immunotherapy with autologous, tumor-lysate-loaded dendritic cells (DCs) on a compassionate use basis using a schedule of three to four weekly DC vaccinations with up to 2 × 10(7) DCs per vaccine, followed by three lysate boosts each 1 month apart.
  
  
  
  Monocyte collections (median age at apheresis 31.5, range 20-143 months) and vaccinations were uneventful without any severe adverse event related to the vaccine, demonstrating feasibility and safety in this very young age group. Two children received immunotherapy during their primary and the remaining five during second- or third-line therapy. Three of seven patients survived long term with a follow-up of 143, 138 and 46 months, with at least two of them harboring somatic mutations. One long-term survivor was vaccinated during primary treatment and the other two after first or second relapse/progression. Two analyzed patients showed positive CD8(+) T-cell responses after vaccination.
  
  
  
  Our data demonstrate that anti-tumor immunotherapy with autologous DCs is feasible and safe in young children with ATRTs and that this approach warrants further investigation in controlled clinical trials.
authors.affiliation: Laboratory of Pediatric Immunology, Department of Microbiology and Immunology, KU Leuven, Belgium, on behalf of the HGG-Immuno network.
authors.forename: Stefaan W
authors.initials: SW
authors.lastname: van Gool
authors.affiliation: Department of Pediatric Hematology and Oncology, Karolinska University Hosital, Karolinska Insitutet, Stockholm, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Holm
authors.affiliation: Stem Cell Laboratory, University Children's Hospital Würzburg, University of Würzburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Rachor
authors.affiliation: Cancer Center Karolinska, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Adamson
authors.affiliation: Stem Cell Laboratory, University Children's Hospital Würzburg, University of Würzburg, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Technau
authors.affiliation: Olgahospital Stuttgart, Children's Hospital, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Maass
authors.affiliation: Children's Hospital Augsburg, Swabian Children's Cancer Center, Klinikum Augsburg, Augsburg, Germany.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Frühwald
authors.affiliation: Stem Cell Laboratory, University Children's Hospital Würzburg, University of Würzburg, Germany; Comprehensive Cancer Center, University Medical Center Würzburg, Germany.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Schlegel
authors.affiliation: Stem Cell Laboratory, University Children's Hospital Würzburg, University of Würzburg, Germany. Electronic address: eyrich_m@ukw.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eyrich
mesh_terms: D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D057176:Compassionate Use Trials; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007223:Infant; D008297:Male; D015166:Monitoring, Immunologic / Q000379:methods; D011379:Prognosis; D012189:Retrospective Studies; D018335:Rhabdoid Tumor / Q000276:immunology / Q000628:therapy*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines
keywords: atypical teratoid-rhabdoid tumor; dendritic cells; immunotherapy; pediatric CNS tumors; therapeutic vaccination