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 >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.

CONCLUSION:

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: Catherine S M Diefenbach, Sacha Gnjatic, Paul Sabbatini, Carol Aghajanian, Martee L Hensley, David R Spriggs, Alexia Iasonos, Helen Lee, Bo Dupont, Sandra Pezzulli, Achim A Jungbluth, Lloyd J Old, Jakob Dupont
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 9 Pg. 2740-8 (May 01 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18451240 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• CTAG1B protein, human
• Cancer Vaccines
• HLA-A Antigens
• Membrane Proteins
• Oleic Acids
• Peptide Fragments
• montanide ISA 51
• Mannitol

Topics

• Adult
• Aged
• Antigens, Neoplasm (administration & dosage, immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (adverse effects, immunology, therapeutic use)
• Female
• HLA-A Antigens (immunology)
• Humans
• Mannitol (administration & dosage, analogs & derivatives, immunology)
• Membrane Proteins (administration & dosage, immunology, metabolism)
• Middle Aged
• Oleic Acids (administration & dosage, immunology)
• Ovarian Neoplasms (immunology, therapy)
• Peptide Fragments (immunology)