title: Generation of a prophylactic melanoma vaccine using whole recombinant yeast expressing MART-1.
abstract: Malignant melanoma is a potentially deadly form of skin cancer and people at high-risk of developing melanoma will benefit from effective preventive intervention. Yeast can be used as an efficient vehicle of antigen loading and immunostimulation. Saccharomyces cerevisiae is not pathogenic to humans and can be easily engineered to express specific antigens. In this study, we have developed a melanoma vaccine using a yeast-based platform expressing a full-length melanocyte/melanoma protein to investigate its utility as a prophylactic melanoma vaccine in a transplantable mouse melanoma model. Yeast was engineered and expanded in vitro without technical difficulties, administered easily with subcutaneous injection, and did not show adverse effects, indicating its practical applicability and favourable safety profile. Despite the lack of knowledge of dominant epitopes of the protein recognized by mouse MHC-class I, the vaccine protected mice from tumor development and induced efficient immune responses, suggesting that the precise knowledge of epitopic sequences and the matched HLA type is not required when delivering a full-length protein using the yeast platform. In addition, the vaccine stimulated both CD4(+) T cells and CD8(+) T cells simultaneously. This study provides a 'proof of principle' that recombinant yeast can be utilized as an effective prophylactic vaccine to target patients at high-risk for melanoma.
authors.affiliation: Department of Dermatology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.
authors.forename: Helge
authors.initials: H
authors.lastname: Riemann
authors.forename: Joe
authors.initials: J
authors.lastname: Takao
authors.forename: Yiqun G
authors.initials: YG
authors.lastname: Shellman
authors.forename: Wirt A
authors.initials: WA
authors.lastname: Hines
authors.forename: Carl K
authors.initials: CK
authors.lastname: Edwards
authors.forename: Alex
authors.initials: A
authors.lastname: Franzusoff
authors.forename: David A
authors.initials: DA
authors.lastname: Norris
authors.forename: Mayumi
authors.initials: M
authors.lastname: Fujita
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D058965:MART-1 Antigen; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D058965:MART-1 Antigen; C548667:MLANA protein, human; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor