title: The antitumor effect of human cord blood-derived dendritic cells modified             by the livin α gene in lung cancer cell lines.
abstract: The growth of malignant tumors is associated with mechanisms of immune escape and inhibition of apoptosis. Livin is a novel member of the inhibitors of apoptosis (IAP) protein family that inhibits cell apoptosis. Livin is specifically expressed by the majority of tumor cells, but it is not expressed in normal adult tissues. In this study, we used umbilical cord blood (UCB)-derived dendritic cells (DCs) infected with a recombinant adenovirus encoding the livin gene as a vaccine to activate effector cells such as cytotoxic T lymphocytes (CTLs) to recognize and kill livin-expressing cancer cells in vitro as an improved strategy for overcoming the ability of these cancer cells to escape apoptosis and antitumor immune responses. We employed interferon-γ (IFN-γ) enzyme-linked immunospot assays to confirm that our immunization strategy induced an antigen-specific reaction to livin and flow cytometric analysis of staining with Annexin V and PI to measure the cytotoxic activity of the effector cells against the livin-expressing lung cancer cell lines A549 and H460. Our results show that the recombinant adenovirus was able to promote the maturation of the UCB-derived DCs. This DC vaccine could activate antigen-specific T cells to produce IFN-γ upon recognition of livin peptide in the context of the appropriate HLA molecule. The antigen-specific T cells mediate significant cytotoxicity against the cancer cells, but are unlikely to cause an autoimmune reaction against the human bronchial epithelia cells (HBE), which do not express livin.
authors.affiliation: Department of Respiratory Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Jin
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Zhang
authors.forename: Wanli
authors.initials: W
authors.lastname: Ma
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Xiong
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Tao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000256:Adenoviridae; D015551:Autoimmunity; D001980:Bronchi / Q000276:immunology / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005312:Fetal Blood; D005822:Genetic Vectors; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D019496:Cancer Vaccines; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D007371:Interferon-gamma