title: Individual patient-specific immunity against high-grade glioma after vaccination with autologous tumor derived peptides bound to the 96 KD chaperone protein.
abstract: OBJECTIVE
  Cancer immunotherapy offers hope of a highly specific nontoxic adjuvant treatment. Heat shock protein peptide complexes (HSPPCs) found in cancer cells carry tumor-specific antigenic proteins and can facilitate adaptive and innate immune responses. Here we show that peptides bound to a 96 kD chaperone protein (HSP-96) from brain tissue containing glioblastoma multiforme (GBM) can be used to safely immunize patients with recurrent GBM.
  
  
  METHODS
  Multimodality immunomonitoring was completed on 12 patients with recurrent GBM before and after immunization with an autologous HSPPC vaccine derived from surgically resected tumor. Clinical endpoints included safety assessments and overall survival.
  
  
  RESULTS
  No adverse events attributable to the vaccine were found. Testing of peripheral blood leukocytes before and after vaccination revealed a significant peripheral immune response specific for the peptides bound to HSP-96, in 11 of the 12 patients treated. Brain biopsies of immune responders after vaccination revealed focal CD4, CD8, and CD56 IFNγ positive cell infiltrates, consistent with tumor site specific immune responses. Immune responders had a median survival of 47 weeks after surgery and vaccination, compared with 16 weeks for the single nonresponder.
  
  
  CONCLUSIONS
  These data provide the first evidence in humans of individual patient-specific immune responses against autologous tumor derived peptides bound to HSP-96.
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco, San Francisco, CA 94141, USA.
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Crane
authors.forename: Seunggu J
authors.initials: SJ
authors.lastname: Han
authors.forename: Brian
authors.initials: B
authors.lastname: Ahn
authors.forename: Jessica
authors.initials: J
authors.lastname: Oehlke
authors.forename: Valerie
authors.initials: V
authors.lastname: Kivett
authors.forename: Anne
authors.initials: A
authors.lastname: Fedoroff
authors.forename: Nicholas
authors.initials: N
authors.lastname: Butowski
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Clarke
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.forename: Michael W
authors.initials: MW
authors.lastname: McDermott
authors.forename: Michael D
authors.initials: MD
authors.lastname: Prados
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Parsa
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005909:Glioblastoma / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D060787:Neoplasm Grading; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D010455:Peptides; C052646:sarcoma glycoprotein gp96 rejection antigens; D007371:Interferon-gamma