title: Recombinant Saccharomyces cerevisiae (yeast-CEA) as a potent activator of murine dendritic cells.
abstract: Recombinant Saccharomyces cerevisiae (yeast) represents a unique and attractive vehicle to deliver antigens in vaccine immunotherapy protocols for cancer or infectious disease, in that it has been shown to be extremely safe and can be administered multiple times to hosts. In the studies reported here, we describe the effects of treatment with recombinant yeast on murine immature dendritic cells (DCs). Yeast expressing human carcinoembryonic antigen (CEA) as a model antigen was studied. Injection of mice subcutaneously with yeast-CEA resulted in rapid increases in MHC class II(+) cells and total antigen-presenting cells in draining lymph nodes. Post-treatment with yeast-CEA, DCs rapidly elevated both MHC class I and class II, numerous costimulatory molecules and other DC maturation markers, and secreted a range of Type I inflammatory cytokines. Gene expression arrays also revealed the rapid up-regulation of numerous cytokine and chemokine mRNAs, as well as genes involved in signal transduction and antigen uptake. Functional studies demonstrated enhanced allospecific reactivity of DCs following treatment with yeast-CEA or control yeast. Additionally, treatment of DCs with yeast-CEA resulted in specific activation of CEA-specific CD8(+) T cells in an MHC-restricted manner in vitro. Lastly, vaccination of CEA-transgenic mice with yeast-CEA elicited antigen-specific CD4(+) and CD8(+) immune responses in vivo. Thus, these studies taken together form a scientific rationale for the use of recombinant yeast in vaccination protocols for cancer or infectious diseases.
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: Michael B
authors.initials: MB
authors.lastname: Bernstein
authors.forename: Mala
authors.initials: M
authors.lastname: Chakraborty
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Wansley
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Guo
authors.forename: Alex
authors.initials: A
authors.lastname: Franzusoff
authors.forename: Sven
authors.initials: S
authors.lastname: Mostböck
authors.forename: Helen
authors.initials: H
authors.lastname: Sabzevari
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: James W
authors.initials: JW
authors.lastname: Hodge
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000628:therapy; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000276:immunology*; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II