Antitumor efficacy of viable tumor vaccine modified by heterogenetic ESAT-6 antigen and cytokine IL-21 in melanomatous mouse

• Published in: Immunologic research 2012-06, Vol.52 (3), p.240-249
• Main Authors: He, Xiangfeng, Wang, Jing, Zhao, Fengshu, Yu, Fangliu, Chen, Dengyu, Cai, Kai, Yang, Cuiping, Chen, Junsong, Dou, Jun
• Format: Article
• Language: English
• Subjects: Adjuvants; Allergology; Animals; Antigens; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Antigens, Bacterial - metabolism; Antitumor activity; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bacterial Proteins - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer vaccines; Cancer Vaccines - genetics; Cancer Vaccines - immunology; Cancer Vaccines - metabolism; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Cytokines; Cytotoxicity; ESAT-6 antigen; gamma -Interferon; Glycosylphosphatidylinositol; Homeobox; Immunological tolerance; Immunology; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interleukin 21; Interleukins - genetics; Interleukins - immunology; Interleukins - metabolism; Internal Medicine; Lung nodules; Medicine/Public Health; Melanoma; Melanoma - genetics; Melanoma - immunology; Melanoma - pathology; Melanoma - therapy; Metastases; Mice; Nodules; Rodents; Survival; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - immunology; Transforming growth factor- beta; Tumors; Vaccination; Vaccines
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/s12026-012-8332-4

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.