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Recognition of naturally processed and ovarian cancer reactive CD8+ T cell epitopes within a promiscuous HLA class II T-helper region of NY-ESO-1

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Abstract

NY-ESO-1 is frequently expressed in epithelial ovarian cancer (EOC) and elicits spontaneous humoral and cellular immune responses in a proportion of EOC patients. The identification of NY-ESO-1 peptide epitopes with dual HLA-class I and class II specificities might be useful in vaccination strategies for generating cognate CD4+ T cell help to augment CD8+ T cell responses. Here, we describe two novel NY-ESO-1-derived MHC class I epitopes from EOC patients with spontaneous humoral immune response to NY-ESO-1. CD8+ T cells derived from NY-ESO-1 seropositive EOC patients were presensitized with a recombinant adenovirus encoding NY-ESO-1or pooled overlapping peptides. These epitopes, ESO127–136 presented by HLA-A68 molecule, and ESO127–135 restricted by HLA-Cw15 allele, are located within ESO119–143, a promiscuous HLA-class II region containing epitopes that bind to multiple HLA-DR alleles. The novel epitopes were naturally processed by APC or naturally presented by tumor cell lines. In addition, these epitopes induced NY-ESO-1-specific CTL in NY-ESO-1 seropositive EOC patients. Together, the results indicate that ESO119–143 epitope has dual HLA classes I and II specificities, and represents a potential vaccine candidate in a large number of cancer patients.

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Acknowledgments

This work was supported by Cancer Research Institute/Ludwig Institute for Cancer Research Cancer Vaccine Collaborative Grant; and by Anna-Marie Kellen Clinical Investigator Award of the Cancer Research Institute, NY (K. O.).

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Correspondence to Kunle Odunsi.

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Matsuzaki, J., Qian, F., Luescher, I. et al. Recognition of naturally processed and ovarian cancer reactive CD8+ T cell epitopes within a promiscuous HLA class II T-helper region of NY-ESO-1. Cancer Immunol Immunother 57, 1185–1195 (2008). https://doi.org/10.1007/s00262-008-0450-4

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