Abstract 2397: SSX-2 vaccines with enhanced MHC class I binding epitopes elicit anti-prostate tumor CTL

Abstract

Abstract The tumor-associated antigen synovial sarcoma X breakpoint 2 (SSX-2) is classified as a cancer-testis antigen (CTA) based upon its tissue-restricted expression to germline cells and its frequent expression in a variety of malignancies. We have previously identified SSX-2 as a potential prostate cancer antigen that can be inducibly expressed in several prostate cancer cell lines. We have also previously identified two nonamer peptides from the amino acid sequence of SSX-2 that have significant affinity for HLA-A2 as assessed by in vitro T2 binding assay. These HLA-2-binding peptides were found to represent HLA-A2-restricted epitopes, able to induce peptide-specific immune responses in peptide- or DNA-immunized HHD-II (HLA-A2.1+/HLA-DR1+ transgenic) mice. Given these observations, the current study was conducted to determine if CTL generated in vaccinated HHD-II mice are capable of lysing HLA-A2+ prostate cancer cells and whether SSX-2 vaccine efficacy could be enhanced using an altered peptide ligand binding strategy. We found that peptides that were designed in silico to have increased or decreased HLA-A2+ affinity had enhanced and reduced HLA-A2 binding by in vitro T2 binding assay, respectively. Additionally, HHD-II mice immunized with modified SSX-2 vaccines developed increased or decreased frequencies of peptide-specific T cells in vivo, which could be detected by IFNγ ELISPOT assay and cytotoxicity assay. Animals immunized with enhancing modified SSX-2 vaccines generated CTL with cross-reactivity to the native SSX-2 epitopes. These CTL were capable of lysing target cells pulsed with both modified and native peptides and could also lyse an HLA-A2-expressing prostate cancer cell line. These results provide support for the further investigation of SSX-2 as an immunotherapeutic target for prostate cancer using vaccines modified to increase MHC class I binding. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2397.