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 Journal Article


Authors: Diefenbach, C. S. M.; Gnjatic, S.; Sabbatini, P.; Aghajanian, C.; Hensley, M. L.; Spriggs, D. R.; Iasonos, A.; Lee, H.; Dupont, B.; Pezzulli, S.; Jungbluth, A. A.; Old, L. J.; Dupont, J.
Article 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: Purpose: The cancer-testis antigen NY-ESO-1 is expressed by »gt;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. Experimental Design: 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. © 2008 American Association for Cancer Research.
Keywords: adult; clinical article; aged; middle aged; clinical trial; fatigue; drug safety; cd8+ t lymphocyte; cd8-positive t-lymphocytes; ovarian neoplasms; metabolism; cancer immunotherapy; progression free survival; ovary cancer; anemia; myalgia; membrane proteins; tumor antigen; cancer regression; immunology; cellular immunity; antigens, neoplasm; cancer vaccine; cancer vaccines; ny eso 1 antigen; immunogenicity; ovary tumor; montanide isa 51; antigen recognition; cancer immunization; peptide fragments; ctag1b protein, human; membrane protein; peptide fragment; drug derivative; phase 1 clinical trial; hyperthyroidism; hypothyroidism; hla a antigen; humoral immunity; mannitol; hla-a antigens; delayed hypersensitivity; oleic acids; injection site pruritus; oleic acid; injection site rash
Journal Title: Clinical Cancer Research
Volume: 14
Issue: 9
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2008-01-01
Start Page: 2740
End Page: 2748
Language: English
DOI: 10.1158/1078-0432.ccr-07-4619
PUBMED: 18451240
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 26" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Jakob Dupont
    64 Dupont
  2. Paul J Sabbatini
    199 Sabbatini
  3. Alexia Elia Iasonos
    179 Iasonos
  4. Martee L Hensley
    220 Hensley
  5. David R Spriggs
    312 Spriggs
  6. Sacha Gnjatic
    111 Gnjatic
  7. Achim Jungbluth
    337 Jungbluth
  8. Bo Dupont
    155 Dupont
  9. Lloyd J Old
    381 Old
  10. Helen Lee
    2 Lee