title: NY-ESO-1 protein glycosylated by yeast induces enhanced immune responses.
abstract: Vaccine strategies that target dendritic cells to elicit potent cellular immunity are the subject of intense research. Here we report that the genetically engineered yeast Saccharomyces cerevisiae, expressing the full-length tumour-associated antigen NY-ESO-1, is a versatile host for protein production. Exposing dendritic cells (DCs) to soluble NY-ESO-1 protein linked to the yeast a-agglutinin 2 protein (Aga2p) protein resulted in protein uptake, processing and MHC class I cross-presentation of NY-ESO-1-derived peptides. The process of antigen uptake and cross-presentation was dependent on the glycosylation pattern of NY-ESO-1-Aga2p protein and the presence of accessible mannose receptors. In addition, NY-ESO-1-Aga2p protein uptake by dendritic cells resulted in recognition by HLA-DP4 NY-ESO-1-specific CD4(+) T cells, indicating MHC class II presentation. Finally, vaccination of mice with yeast-derived NY-ESO-1-Aga2p protein led to an enhanced humoral and cellular immune response, when compared to the bacterially expressed NY-ESO-1 protein. Together, these data demonstrate that yeast-derived full-length NY-ESO-1-Aga2p protein is processed and presented efficiently by MHC class I and II complexes and warrants clinical trials to determine the potential value of S. cerevisiae as a host for cancer vaccine development.
authors.affiliation: Department of Oncology, Universtity Hospital Zurich, University of Zurich/Irchel, Zurich, Switzerland. andreas.wadle@usz.ch
authors.forename: Andreas
authors.initials: A
authors.lastname: Wadle
authors.forename: Axel
authors.initials: A
authors.lastname: Mischo
authors.forename: Sabine
authors.initials: S
authors.lastname: Strahl
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Gerhard
authors.initials: G
authors.lastname: Held
authors.forename: Frank
authors.initials: F
authors.lastname: Neumann
authors.forename: Beate
authors.initials: B
authors.lastname: Wullner
authors.forename: Eliane
authors.initials: E
authors.lastname: Fischer
authors.forename: Sascha
authors.initials: S
authors.lastname: Kleber
authors.forename: Julia
authors.initials: J
authors.lastname: Karbach
authors.forename: Elke
authors.initials: E
authors.lastname: Jager
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.forename: Protul A
authors.initials: PA
authors.lastname: Shrikant
authors.forename: Alexander
authors.initials: A
authors.lastname: Knuth
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Christoph
authors.initials: C
authors.lastname: Renner
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006031:Glycosylation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: C543385:AGA2 protein, S cerevisiae; D000906:Antibodies; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins