title: Safety and immunogenicity study of NY-ESO-1b peptide and montanide ISA-51 vaccination of patients with epithelial ovarian cancer in high-risk first remission.
abstract: OBJECTIVE
  The cancer-testis antigen NY-ESO-1 is expressed by >40% of advanced epithelial ovarian cancers and is a promising immunotherapeutic target. In this study, we describe the effects of vaccination with the HLA-A*0201-restricted NY-ESO-1b peptide on patients with epithelial ovarian cancer in high-risk first remission.
  
  
  METHODS
  After primary surgery and chemotherapy, high-risk epithelial ovarian cancer patients in first clinical remission received NY-ESO-1b peptide and Montanide every 3 weeks for five vaccinations. Tumor expression was evaluated by immunohistochemistry. Toxicity was monitored using National Cancer Institute Common Toxicity Criteria Scale Version 2. NY-ESO-1 specific humoral immunity (ELISA), T-cell immunity (tetramer and ELISPOT), and delayed-type hypersensitivity were assessed on weeks 0, 1, 4, 7, 10, 13, and 16.
  
  
  RESULTS
  Treatment-related adverse events included grade 1 fatigue, anemia, pruritus, myalgias, and hyperthyroidism and grade 2 hypothyroidism. There were no grade 3/grade 4 adverse events. Three of four patients (75%) with NY-ESO-1-positive tumor showed T-cell immunity by tetramer (0.6-9.5%) and ELISPOT (range, 35-260 spots). Four of five patients (80%) with NY-ESO-1-negative tumor showed T-cell immunity by tetramer (1.0-12.1%) and/or ELISPOT (range, 35-400 spots). With a median follow-up of 11.3 months, six of nine patients (67%) have recurred, with a median progression-free survival of 13 months (95% confidence interval, 11.2 months-not reached). Three of nine patients remain in complete clinical remission at 25, 38, and 52 months.
  
  
  CONCLUSIONS
  Vaccination of high-risk HLA-A*0201-positive epithelial ovarian cancer patients with NY-ESO-1b and Montanide has minimal toxicity and induces specific T-cell immunity in patients with both NY-ESO-1-positive and NY-ESO-1-negative tumors. Additional study is warranted.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center,New York, New York 10021, USA. magicdc@mskcc.org
authors.forename: Catherine S M
authors.initials: CS
authors.lastname: Diefenbach
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Paul
authors.initials: P
authors.lastname: Sabbatini
authors.forename: Carol
authors.initials: C
authors.lastname: Aghajanian
authors.forename: Martee L
authors.initials: ML
authors.lastname: Hensley
authors.forename: David R
authors.initials: DR
authors.lastname: Spriggs
authors.forename: Alexia
authors.initials: A
authors.lastname: Iasonos
authors.forename: Helen
authors.initials: H
authors.lastname: Lee
authors.forename: Bo
authors.initials: B
authors.lastname: Dupont
authors.forename: Sandra
authors.initials: S
authors.lastname: Pezzulli
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Jakob
authors.initials: J
authors.lastname: Dupont
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D008565:Membrane Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D009829:Oleic Acids / Q000008:administration & dosage / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D015234:HLA-A Antigens; D008565:Membrane Proteins; D009829:Oleic Acids; D010446:Peptide Fragments; C477385:montanide ISA 51; D008353:Mannitol