title: Dendritic cell generated from CD34+ hematopoietic progenitors can be transfected with adenovirus containing gene of HBsAg and induce antigen-specific cytotoxic T cell responses.
abstract: Dendritic cells (DCs) are professional antigen presenting cells that are being considered as potential immunotherapeutic agents to promote host immune responses against tumor antigens. The use of such modified antigen-presenting cells for research or therapeutic have been limited by several factors, including maintaining DCs in a highly activated state, efficient transduction and expression, stable expression, identification of appropriate tumor-associated antigens, and absence of unintended functional changes or cytotoxicity. In this study, the feasibility of using CD34-DCs for tumor immunotherapy after transduction with a recombinant adenovirus containing HBsAg gene (AdVHBsAg), an HCC-associated antigen, was investigated. The gene transfer with recombinant adenovirus vectors (AdV) can obtained high levels of stable expression of HBsAg and its efficiency was increased in a multiplicity of infection (MOI)-dependent manner. Moreover, the AdVHBsAg infection had no appreciable effect on apoptosis of DCs compared with that of mock-infected DCs. The T cell lines, primed by the recombinant AdVHBsAg-infected DCs in vitro, recognized HBsAg-expressing tumor cell lines in a human leukocyte antigen (HLA) class I-restricted manner, and evoked a higher CTL response, which indicated that high potent and specific antitumor immune response could be induced by AdVHBsAg DC vaccine. It may be a promising the therapeutic modality for the treatment of HBsAg-expressing tumors, and will be a foundation for further study on DC vaccines and gene therapy for HCC.
authors.affiliation: Department of Oncology, Xijing Hospital, Fourth Military Medical University, Xian, Shaanxi Province 710032, China.
authors.forename: Jing-Yue
authors.initials: JY
authors.lastname: Yang
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Cao
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Liu
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zhang
authors.forename: Zeng-Hui
authors.initials: ZH
authors.lastname: Teng
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D018952:Antigens, CD34 / Q000378:metabolism*; D017209:Apoptosis; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D018952:Antigens, CD34; D006514:Hepatitis B Surface Antigens; D011994:Recombinant Proteins; D007371:Interferon-gamma