1. Human dendritic cell maturation and activation by a heat-killed recombinant yeast (Saccharomyces cerevisiae) vector encoding carcinoembryonic antigen
- Author
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Remondo, Cinzia, Cereda, Vittore, Mostböck, Sven, Sabzevari, Helen, Franzusoff, Alex, Schlom, Jeffrey, and Tsang, Kwong-Y.
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DENDRITIC cells , *SACCHAROMYCES cerevisiae , *CARCINOEMBRYONIC antigen , *IMMUNOGENETICS , *GENE expression , *CANCER immunotherapy , *TRANSGENES , *GENETIC code , *CHEMOKINES - Abstract
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-α, IFN-γ, IL-8, IL-2, IL-13, IL-10, and IL-1β. 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. [Copyright &y& Elsevier]
- Published
- 2009
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