|Induction of specific human cytotoxic T cells using dendritic cells transduced with an adenovector encoding rat epidermal growth factor receptor 2|
Authors: Kalathil Suresh, Elizabeth Scheid, Laurence Klotz, Vasundara Venkateswaran, Jack Gauldie, Ronan Foley
Affiliations: Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada, Juravinski Hospital, 2nd Floor Laboratory, 711 Concession St, Hamilton, Ontario, L8V 1C3, Canada
Published online on: Thursday, July 14, 2011
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-γ mRNA. In ELISPOT and intracellular cytokine staining (ICS) assays, CD8+ CTLs induced by Adv-HER2 transduced DCs released IFN-γ 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.