Human dendritic cell maturation and activation by a heat-killed recombinant yeast (Saccharomyces cerevisiae) vector encoding carcinoembryonic antigen.
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.
Remondo
Cinzia
C
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cereda
Vittore
V
Mostböck
Sven
S
Sabzevari
Helen
H
Franzusoff
Alex
A
Schlom
Jeffrey
J
Tsang
Kwong-Y
KY
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
D015703:Antigens, CD; D002272:Carcinoembryonic Antigen; D016207:Cytokines