title: Cancer stem cell vaccine expressing ESAT-6-gpi and IL-21 inhibits melanoma growth and metastases.
abstract: Tumor vaccines may induce antitumor efficacy, however, weak immunogenicity of tumor antigens is one of the prime obstacles for excitation of the antitumor immune responses. Therefore, strategies that enhance immunogenicity of tumor vaccines are of particular interest. In this study, a novel melanoma B16F10 CD133(+)CD44(+) cancer stem cell (CSC) vaccine expressing 6 kDa early secreted antigenic target (ESAT-6) in the glycosylphosphatidylinositol (GPI)-anchored form and secreting interleukin (IL)-21 was developed. Its anti-melanoma efficacy and mechanisms were investigated in mice. The results demonstrated that the B16F10-ESAT-6-gpi/IL-21 CD133(+)CD44(+) CSC vaccine exhibited enhanced anti-melanoma efficacy as determined by inhibited melanoma growth, prolonged survival of melanoma bearing mice. The anti-melanoma immunity was associated with elevated levels of serum anti-ESAT-6 and interferon (IFN)-γ as well as increased cytotoxic activities of natural killer cells, splenocytes, and complement dependent cytotoxicity. Furthermore, this CSC-based vaccine apparently inhibited melanoma lung metastasis by decreasing the level of Vimentin while increasing the level of E-cadherin expression, suggesting an inhibited epithelial mesenchymal transition. Thus, the B16F10-ESAT-6-gpi/IL-21 CD133(+)CD44(+) CSC vaccine may be used to reactivate the anti-tumor immunity and for treatment of melanoma.
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Fengshu
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Affiliated Tumor Hospital of Nantong University Nantong 226361, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Jianan
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Pan
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Songyan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University Nanjing 210009, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Dou
keywords: ESAT-6; Melanoma; cancer stem cell vaccine; cancer stem cells; interleukin-21