NY‐ESO‐1 protein glycosylated by yeast induces enhanced immune responses

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 product...

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Published in:	Yeast Vol. 27; no. 11; pp. 919 - 931
Main Authors:	Wadle, A, Mischo, A, Strahl, S, Nishikawa, H, Held, G, Neumann, F, Wullner, B, Fischer, E, Kleber, S, Karbach, J, Jager, E, Shiku, H, Odunsi, K, Shrikant, P A, Knuth, A, Cerundolo, V, Renner, C
Format:	Journal Article
Language:	English
Published:	Chichester, UK Wiley 01.11.2010 John Wiley & Sons, Ltd
Subjects:	10032 Clinic for Oncology and Hematology 1303 Biochemistry 1305 Biotechnology 1311 Genetics 1502 Bioengineering 2402 Applied Microbiology and Biotechnology 610 Medicine & health administration & dosage Animals Antibodies Antibodies - blood Antigen Presentation antigens Antigens, Neoplasm Antigens, Neoplasm - genetics Antigens, Neoplasm - immunology Antigens, Neoplasm - metabolism blood Cancer Vaccines Cancer Vaccines - administration & dosage Cancer Vaccines - immunology CD4 antigen CD4-Positive T-Lymphocytes CD4-Positive T-Lymphocytes - immunology Cell Adhesion Molecules Cell Adhesion Molecules - genetics Cell Adhesion Molecules - immunology Cell Adhesion Molecules - metabolism cell-mediated immunity Cells, Cultured Clinical trials cross‐presentation cytotoxic T cells Data processing Dendritic Cells Dendritic Cells - immunology Female Genetic engineering genetically engineered microorganisms genetics Glycosylation Histocompatibility antigen HLA Humans immune response Immune response (humoral) Immunity (cell-mediated) immunology Lymphocytes T Major histocompatibility complex Mannose receptors Membrane Proteins Membrane Proteins - genetics Membrane Proteins - immunology Membrane Proteins - metabolism metabolism MHC Mice Mice, Inbred C57BL NY-ESO-1 protein peptide processing peptides receptors Recombinant Fusion Proteins Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - immunology Recombinant Fusion Proteins - metabolism Saccharomyces cerevisiae Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - immunology Saccharomyces cerevisiae Proteins - metabolism T-lymphocytes vaccination vaccine development yeast yeasts
ISSN:	0749-503X, 1097-0061, 1097-0061
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Summary:	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. Copyright © 2010 John Wiley & Sons, Ltd.
Bibliography:	These authors contributed equally to this study. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0749-503X 1097-0061 1097-0061
DOI:	10.1002/yea.1796