title: Antitumor efficacy of viable tumor vaccine modified by heterogenetic ESAT-6 antigen and cytokine IL-21 in melanomatous mouse.
abstract: The goal of this study was to investigate whether glycosylphosphatidylinositol (GPI)-anchored 6 kDa early secreted antigenic target (ESAT-6) and IL-21-producing B16F10/ESAT-6-GPI-IL-21 viable vaccine would induce antitumor efficacy. Mice were immunized with B16F10/ESAT-6-GPI-IL-21 vaccine and challenged by B16F10 cells 2 weeks later. Antitumor efficacy and mechanisms of the vaccine were analyzed. Vaccination with the viable B16F10/ESAT-6-GPI-IL-21 vaccine resulted in an increase of IFN-γ level and the CD8(+)CTL cytotoxicity, a decrease in TGF-β generation and increase in the expression of miR-200c that serves as melanoma suppressor by directly targeting zinc-finger E-box binding homeobox 1 to inhibit epithelial-mesenchymal transition and block tumor metastasis. The vaccine significantly inhibited the melanoma growth, reduced the lung melanoma nodules, and prolonged the mouse survival compared with the controls. These findings highlighted IL-21 as an immune adjuvant in an engineered viable tumor vaccine to reinforce heterogenetic antigen ESAT-6 immune tolerance break to induce powerful antitumor efficacy in mice.
authors.affiliation: Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Nanjing, 210009, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Fengshu
authors.initials: F
authors.lastname: Zhao
authors.forename: Fangliu
authors.initials: F
authors.lastname: Yu
authors.forename: Dengyu
authors.initials: D
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Cai
authors.forename: Cuiping
authors.initials: C
authors.lastname: Yang
authors.forename: Junsong
authors.initials: J
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Dou
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D000098546:Interleukin-21
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D019496:Cancer Vaccines; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007378:Interleukins; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D000098546:Interleukin-21