title: Recombinant adenovirus of SEA and CD80 genes driven by MMRE and mouse TERT promoter induce effective antitumor immune responses against different types of tumor cells in vitro and in vivo.
abstract: Staphylococcus enterotoxin A (SEA) is a powerful immunostimulant and can stimulate T cells bearing certain T-cell receptor β-chain variable regions when bound to major histocompatibility complex II molecules. SEA is widely used in research of antitumor therapy. The low affinity T-cell receptor (TCR) interaction with SEA in the absence of MHC class II antigens is sufficient for the induction of cytotoxicity but requires additional CD28/B7 signaling to result in proliferation of resting T cells. In this study, we constructed recombinant adenovirus (named as Ad-MMRE-mTERT-BIS) carrying membrane-expressing SEA (named as SEAtm) and CD80 driven by Myc-Max response elements (MMRE) and mouse telomerase reverse transcriptase (mTERT) promoter to reduce toxicity and to improve safety and efficiency. We demonstrated that Ad-MMRE-mTERT-BIS could make SEAtm and CD80 to co-express highly on the surface of Hepa1-6 and B16 cells, at low level on the surface of CT26 cells, but not in NIH3T3. Hepa1-6 and B16 cells infected by the recombinant adenovirus induced proliferation of CD4+ and CD8+ T cells and increased cytokine [interleukin (IL)-2, tumor necrosis factor (TNF)-α, interferon (IFN)-γ] production in vitro. Intratumoral injection of Ad-MMRE-mTERT-BIS in hepatoma and melanoma mouse models induced tumor-specific cytotoxic T cells in the spleen. Moreover, hepatoma and melanoma xenografts were suppressed by treatment with Ad-MMRE-mTERT-BIS and the survival time of treated mice was prolonged. These findings suggest that recombinant adenovirus of SEA and CD80 genes driven by mTERT promoter could induce effective antitumor immune responses against different kinds of tumor cells in vitro and in vivo.
authors.affiliation: Center for Special Medicine and Experimental Research, 306th Hospital of PLA, Beijing 100101, P.R. China.
authors.forename: Shao-Yan
authors.initials: SY
authors.lastname: Si
authors.affiliation: Center for Special Medicine and Experimental Research, 306th Hospital of PLA, Beijing 100101, P.R. China.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Liu
authors.affiliation: Department of Dermatology, 306th Hospital of PLA, Beijing 100101, P.R. China.
authors.forename: Jun-Lian
authors.initials: JL
authors.lastname: Liu
authors.affiliation: Center for Special Medicine and Experimental Research, 306th Hospital of PLA, Beijing 100101, P.R. China.
authors.forename: Bing-Xin
authors.initials: BX
authors.lastname: Xu
authors.affiliation: Center for Special Medicine and Experimental Research, 306th Hospital of PLA, Beijing 100101, P.R. China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Li
authors.affiliation: Center for Special Medicine and Experimental Research, 306th Hospital of PLA, Beijing 100101, P.R. China.
authors.forename: Ya-Ya
authors.initials: YY
authors.lastname: Qin
authors.affiliation: Center for Special Medicine and Experimental Research, 306th Hospital of PLA, Beijing 100101, P.R. China.
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Song
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009374:Neoplasms, Experimental / Q000276:immunology*; D020218:Response Elements; D019098:Telomerase; D016896:Treatment Outcome
chemical_list: D018122:B7-1 Antigen; D016207:Cytokines; D004768:Enterotoxins; C026066:enterotoxin A, Staphylococcal; D019098:Telomerase; C509187:Tert protein, mouse