Cancer Immunity 3:16 (2003)

Essential roles of tumor-derived helper T cell epitopes for an effective peptide-based tumor vaccine

Lijie Wang¹, Yoshihiro Miyahara¹, Takuma Kato², Linan Wang², Takumi Aota¹, Kagemasa Kuribayashi², and Hiroshi Shiku¹

¹Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, 514-8507, Japan
²Department of Bioregulation, Mie University School of Medicine, Tsu, Mie, 514-8507, Japan

Keywords: mice, vaccination, immunological monitoring, cytotoxic T cells

Abstract

In this study, we identified a c-erbB-2/HER2/neu (HER2)-derived Th epitope (HER2_16-30) and examined the role of Th epitopes in HER2-specific CD8+ T cell induction and in vivo tumor eradication, with a particular emphasis on the role of tumor cell-derived Th epitopes. Immunization of BALB/c mice using a mixture of Th epitope HER2_16-30 and CTL epitope HER2_63-71 administered subcutaneously with murine GM-CSF (mGM-CSF) induced a much higher level of HER2_63-71-specific CD8+ T cells compared with that obtained with the CTL epitope alone. HER2-unrelated OVA-derived Th epitope (OVA_323-339) exhibited a similar enhancing effect on HER2_63-71-specific CD8+ T cell induction. However, only mice immunized with HER2_16-30 and HER2_63-71, but not with a tumor-unrelated OVA_323-339 and HER2_63-71, showed in vivo eradication of CMS5mHE tumor cells expressing HER2 but not OVA. This distinction was observed in preventative as well as therapeutic experimental settings. Conversely, both HER2_16-30 and OVA_323-339 Th epitopes were equally effective in inducing the eradication of CMS5mHEOVA tumor cells which express HER2 as well as OVA. Our results clearly indicate that CTL and Th epitopes of target tumor cell origin should be used for effective induction of in vivo antitumor immunity.