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

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, ESO_157–170, 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 ESO_157–170 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.