Abstract 2688: Establishment of high avidity CTL clones induced by HLA-A2 restricted glypican-3 (GPC3) peptide vaccine

Abstract

Abstract Glypican-3 (GPC3) is an onco-fetal antigen which is overexpressed in human hepatocellular carcinoma (HCC) and that among normal tissues it is slightly expressed in placenta and embryonic liver. Previously, we have identified a HLA-A2-restricted GPC3144-152 (FVGEFFTDV) peptide which can induce GPC3-reactive cytotoxic T lymphocytes (CTLs) without inducing autoimmunity. In the present study, we performed phase I clinical trial of HLA-A2 restricted GPC3-derived peptide vaccine to the 14 patients with advanced HCC. Immunological responses were analyzed by ex vivo IFN-γ Enzyme-linked immunospot (ELISPOT) assay. The frequency of GPC3 peptide specific CTLs after vaccinations (mean, 96; range, 5-441) was statistically significantly larger than that before vaccination (mean, 6.5; range, 0-43) (P < 0.01). An increase of the GPC3 peptide specific CTL frequency was detected in 12 (86%) of 14 patients after vaccination. Additionally, there was a significant correlation between the maximum value of GPC3 peptide specific CTLs after vaccination and dose of peptide injected (P = 0.0166, r = 0.665). Moreover, we established some GPC3 peptide specific CTL clones from PBMCs of patients vaccinated with GPC3 peptide by single cell sort using Dextramer and CD107a antibody. These CTL clones were high avidity CTLs (10−10M and 10−11M) and could recognize HCC cell lines expressing GPC3 in a HLA-class I-restricted manner. These results suggest that tumor-cytolytic T cells are indeed elicited in patients after vaccination. Now we investigate whether the GPC3 based immunotherapy have possibility of the application for other GPC3 expressing cancers including melanoma, clear cell carcinoma of the ovary, pediatric cancer or not, using established GPC3 peptide specific CTL clone. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2688. doi:10.1158/1538-7445.AM2011-2688