Journal
IMMUNOLOGIC RESEARCH
Volume 52, Issue 3, Pages 240-249Publisher
HUMANA PRESS INC
DOI: 10.1007/s12026-012-8332-4
Keywords
Melanoma; Tumor vaccine; 6 kDa early secreted antigenic target; Interleukin-21; Glycosylphosphatidylinositol
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Funding
- National Natural Science Foundation of China [81071769]
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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-gamma level and the CD8(+)CTL cytotoxicity, a decrease in TGF-beta 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.
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