Induction Of Specific Human Cytotoxic T Cells Using Dendritic Cells Transduced With An Adenovector Encoding Rat Epidermal Growth Factor Receptor 2

This study demonstrates the ability to generate antigen-specific cytotoxic T cells (CTLs) against HER2 using a xenoantigenic immune stimulation strategy. Dendritic cells (DCs) were transduced with an adenovirus vector incorporating full-length cDNA for rat (xenoantigen) epidermal growth factor receptor 2 (Adv-HER2). Stimulation of autologous T cells with Adv-HER2 infected DCs led to enhanced HER2-specific reactivity as assessed by quantitative real-time polymerase chain reaction (qRT-PCR) for T cell IFN-gamma mRNA. In ELISPOT and intracellular cytokine staining (ICS) assays, CD8(+) CTLs induced by Adv-HER2 transduced DCs released IFN-gamma following stimulation with irradiated autologous DCs infected with Adv-HER2 or loaded with a human prostate cancer cell line (LNCaP) lysate. DCs pulsed with HER2 peptides were less stimulatory than Adv-HER2 transduced DCs. HER2 DC induced CTL lysed HER2(+) HLA-A2(+) tumor cells (MCF-7); significantly reduced lysis occurred in HER2(+) HLA-A2(-) tumor cells (SKOV-3), and the NK cell sensitive cell line K-562.