title: Induction of specific human cytotoxic T cells using dendritic cells transduced with an adenovector encoding rat epidermal growth factor receptor 2.
abstract: 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.
authors.affiliation: Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
authors.forename: Kalathil
authors.initials: K
authors.lastname: Suresh
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Scheid
authors.forename: Laurence
authors.initials: L
authors.lastname: Klotz
authors.forename: Vasundara
authors.initials: V
authors.lastname: Venkateswaran
authors.forename: Jack
authors.initials: J
authors.lastname: Gauldie
authors.forename: Ronan
authors.initials: R
authors.lastname: Foley
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; D018719:Erb-b2 Receptor Tyrosine Kinases