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

Catherine S.M. Diefenbach, Sacha Gnjatic, Paul Sabbatini, Carol Aghajanian, Martee L. Hensley, David R. Spriggs, Alexia Lasonos, Helen Lee, Bo Dupont, Sandra Pezzulli, Achim A. Jungbluth, Lloyd J. Old, Jakob Dupont

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101 Scopus citations

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.

Original languageEnglish
Pages (from-to)2740-2748
Number of pages9
JournalClinical Cancer Research
Volume14
Issue number9
DOIs
StatePublished - 1 May 2008
Externally publishedYes

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