Two novel squamous cell carcinoma antigen-derived HLA-A *0201-binding peptides induce in vitro and in vivo CD8 + cytotoxic T lymphocyte responses

Abstract

Squamous cell carcinoma antigen (SCCA) is overexpressed in many squamous cell cancers and SCCA-derived peptide-specific CD8+ cytotoxic T lymphocytes can display cytotoxicity against tumor cells. In the present study, we screened the SCCA amino acid sequence for potential HLA-A *0201-binding CD8+ T-cell epitopes using tw - predictive computational algorithms. Seven epitope candi dates were selected of which SCCA246254(LLPNEIDGL), SCCA223-231(SLEDVQAKV), SCCA328-336(VLHKAFVEV) and SCCA324-332(VLSGVLHKA) significantly stabilized HLA-A*0201 molecules on T2 cells. Both SCCA328-336 and SCCA324-332 induced CD8+ IFN-γ+ T-cell responses in HLA-A*0201-positive peripheral blood mononuclear cells as assessed by intracellular cytokine staining. C CAistent with this, immunization with either SCCA328-336 or SCCA324-332 effectively elicited CD8+ IFN-γ+ T cells in HLA-A*0201 transgenic mice as visualized by IFN-γ ELISPOT assay and intracellular in vitro cytokine staining. Furthermore, CD8+ T cells induced in vitro or in vivo by SCCA328-336 or SCCA324-332 demonstrated in vitro cytotoxicity against peptide-pulsed T2 cells and splenocytes, respectively. These novel SCCA-derived CD8+ T-cell epitopes described, herein, may be potentially important components for diagnostic reagents and immunotherapeutic vaccines for the treatment of squamous cell carcinomas.