title: Immuno-gene therapy of melanoma by tumor antigen epitope modified IFN-gamma.
abstract: Cytokine-based vaccines play a major part in tumor immuno-gene therapy. However, down-regulated antigen expression on tumor cells may diminish the immuno-potentiating aspects of cellular vaccines. In this study, we coexpressed a tumor antigen epitope with IFN-gamma in the same gene by replacing the IFN-gamma signal peptide with an antigen epitope-expressing signal peptide. We then investigated the effect of the antigen epitope-incorporated IFN-gamma on the immunotherapy of murine melanoma B16 tumors. Results showed that TRP-2 epitope-expressing IFN-gamma decreased B16 tumorigenicity and enhanced its immunogenicity after gene transfer. Protective immunity against wild type B16 tumors was induced by vaccination with IFN-gamma transiently gene-modified tumor cells. These data suggest that cellular vaccines engineered to express an antigen epitope within an immunostimulatory cytokine could potentiate the immunization effect.
authors.affiliation: Gene Therapy Group, Department of Microbiology and Immunology, Arizona Health Sciences Center, University of Arizona, Tucson, 245049, AZ 85724, USA.
authors.forename: Xianghui
authors.initials: X
authors.lastname: He
authors.forename: Phoebe
authors.initials: P
authors.lastname: Luo
authors.forename: Tom C
authors.initials: TC
authors.lastname: Tsang
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: David T
authors.initials: DT
authors.lastname: Harris
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation; D000939:Epitopes; D015316:Genetic Therapy; D006680:HLA Antigens / Q000276:immunology; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000662:veterinary; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D012878:Skin Neoplasms / Q000276:immunology* / Q000662:veterinary
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D016207:Cytokines; D000939:Epitopes; D006680:HLA Antigens; D007371:Interferon-gamma
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