Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer

Kunle Odunsi, Feng Qian, Junko Matsuzaki, Paulette Mhawech-Fauceglia, Christopher Andrews, Eric W. Hoffman, Linda Pan, Gerd Ritter, Jeannine Villella, Bridget Thomas, Kerry Rodabaugh, Shashikant Lele, Protul Shrikant, Lloyd J. Old, Sacha Gnjatic

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191 Scopus citations

Abstract

NY-ESO-1 is a "cancer-testis" antigen expressed in epithelial ovarian cancer (EOC) and is among the most immunogenic tumor antigens defined to date. The NY-ESO-1 peptide epitope, ESO157-170, is recognized by HLA-DP4-restricted CD4+ T cells and HLA-A2- and A24-restricted CD8+ T cells. To test whether providing cognate helper CD4 + T cells would enhance the antitumor immune response, we conducted a phase I clinical trial of immunization with ESO157-170 mixed with incomplete Freund's adjuvant (Montanide ISA51) in 18 HLA-DP4+ EOC patients with minimal disease burden. NY-ESO-1-specific Ab responses and/or specific HLA-A2-restricted CD8+ and HLA-DP4-restricted CD4 + T cell responses were induced by a course of at least five vaccinations at three weekly intervals in a high proportion of patients. There were no serious vaccine-related adverse events. Vaccine-induced CD8+ and CD4+ T cell clones were shown to recognize NY-ESO-1-expressing tumor targets. T cell receptor analysis indicated that tumor-recognizing CD4+ T cell clones were structurally distinct from non-tumor-recognizing clones. Long-lived and functional vaccine-elicited CD8+ and CD4+ T cells were detectable in some patients up to 12 months after immunization. These results confirm the paradigm that the provision of cognate CD4+ T cell help is important for cancer vaccine design and provides the rationale for a phase II study design using ESO 157-170 epitope or the full-length NY-ESO-1 protein for immunotherapy in patients with EOC.

Original languageEnglish (US)
Pages (from-to)12837-12842
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number31
DOIs
StatePublished - Jul 31 2007

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Keywords

  • HLA-DP4
  • Peptide epitope
  • Tumor recognition
  • Vaccine

ASJC Scopus subject areas

  • General

Cite this

Odunsi, K., Qian, F., Matsuzaki, J., Mhawech-Fauceglia, P., Andrews, C., Hoffman, E. W., Pan, L., Ritter, G., Villella, J., Thomas, B., Rodabaugh, K., Lele, S., Shrikant, P., Old, L. J., & Gnjatic, S. (2007). Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer. Proceedings of the National Academy of Sciences of the United States of America, 104(31), 12837-12842. https://doi.org/10.1073/pnas.0703342104