Dendritic cell generated from CD34+ hematopoietic progenitors can be transfected with adenovirus containing gene of HBsAg and induce antigen-specific cytotoxic T cell responses.
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.
Yang
Jing-Yue
JY
Department of Oncology, Xijing Hospital, Fourth Military Medical University, Xian, Shaanxi Province 710032, China.
Cao
Da-Yong
DY
Liu
Wen-Chao
WC
Zhang
Hong-Mei
HM
Teng
Zeng-Hui
ZH
Ren
Jun
J
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
D018952:Antigens, CD34; D006514:Hepatitis B Surface Antigens; D011994:Recombinant Proteins; D007371:Interferon-gamma