title: [Generation of antitumor response against hepatocellular carcinoma by in vitro transduction of dendritic cells with adeno-associated virus expressing α-fetoprotein].
abstract: OBJECTIVE
  To investigate the generation of antitumor response against hepatocellular carcinoma by in vitro transduction of dendritic cells (DC) with recombinant adeno-associated virus expressing α-fetoprotein (rAAV-AFP).
  
  
  METHODS
  Peripheral blood mononuclear cells were isolated from healthy volunteers. Adherent peripheral blood mononuclear cells were transduced with AAV-AFP and cultured in the presence of granulocyte macrophage colony stimulating factor and interleukin-4 to generate dendritic cells. MTS assay was used to measure the ability of DC transduced with AAV-AFP (AAV-AFP + DC) to stimulate the proliferation of T cell. The phenotype and AFP protein expression of DC and the secretion of IFN (interferon)-γ and IL (interleukin)-4 by T cells were detected by flow cytometry. The killing efficacy of cytotoxic T lymphocytes (CTL) activated by AAV-AFP + DC against AFP positive hepatocellular carcinoma cell lines was detected by lactate dehydrogenase (LDH) release assay.
  
  
  RESULTS
  AAV-AFP + DC expressed HLAI (97.12%), HLAII (97.32%), CD80 (38.94%), CD83 (60.84%) and CD86 (98.14%). AFP was secreted by 81.2% of AAV-AFP + DC. And it could stimulate effectively the proliferation of T cell. 19.84% of CD4(+)T cells and 18.65% of CD8(+)T cells activated by AAV-AFP + DC produced IFN-γ but not IL-4 and showed distinct killing activities against AFP positive hepatocellular carcinoma cell lines HepG2 (56.45%) and BEL7402 (78.84%).
  
  
  CONCLUSIONS
  AAV-AFP + DC can elicit distinct antitumor responses against AFP positive hepatocellular carcinoma cell lines so as to provide a basis for further researches on the clinical application of AAV-AFP + DC in the treatment of hepatocellular carcinoma.
authors.affiliation: Department of Gastroenterology, Shandong Yantai Haigang Hospital, Shandong Yantai, China. duwenzhen1970@sina.com
authors.forename: Wen-zhen
authors.initials: WZ
authors.lastname: Du
authors.forename: Tian-xia
authors.initials: TX
authors.lastname: Yu
mesh_terms: D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic; D000509:alpha-Fetoproteins / Q000096:biosynthesis*
chemical_list: C508598:IL4 protein, human; D000509:alpha-Fetoproteins; D015847:Interleukin-4; D007371:Interferon-gamma