title: Human dendritic cell maturation and activation by a heat-killed recombinant yeast (Saccharomyces cerevisiae) vector encoding carcinoembryonic antigen.
abstract: Tumor-associated antigens are weakly immunogenic. Human carcinoembryonic antigen (CEA) is overexpressed on a wide range of human carcinomas and represents an attractive target for cancer immunotherapy. This study analyzes the ability of a Saccharomyces cerevisiae vector containing the transgene encoding CEA (yeast-CEA) to activate human dendritic cells (DCs) and stimulate CEA-specific T-cell responses. We demonstrate for the first time that treatment with yeast-CEA can activate human DCs, resulting in increases in surface expression of CD80, CD83, CD54, CD58, and MHC class II, and increased production by DCs of IL-12p70, TNF-alpha, IFN-gamma, IL-8, IL-2, IL-13, IL-10, and IL-1beta. We also show that human DCs treated with yeast-CEA can activate CEA-specific T-cell lines and can act as antigen-presenting cells (APCs) to generate CEA-specific T-cell lines capable of lysing CEA(+) human tumor cells. Gene expression profiles of human DCs treated with yeast-CEA show increased expression of numerous genes involved in the production of chemokines and cytokines and their receptors, and genes related to antigen uptake, antigen presentation, and signal transduction.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Remondo
authors.forename: Vittore
authors.initials: V
authors.lastname: Cereda
authors.forename: Sven
authors.initials: S
authors.lastname: Mostböck
authors.forename: Helen
authors.initials: H
authors.lastname: Sabzevari
authors.forename: Alex
authors.initials: A
authors.lastname: Franzusoff
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: Kwong-Y
authors.initials: KY
authors.lastname: Tsang
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D008213:Lymphocyte Activation; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D015703:Antigens, CD; D002272:Carcinoembryonic Antigen; D016207:Cytokines