title: Induction of antigen-specific immune responses by dendritic cells transduced with a recombinant lentiviral vector encoding MAGE-A3 gene.
abstract: OBJECTIVE
  Melanoma antigen gene A3 (MAGE-A3) is aberrantly expressed in a number of cancer types. Because of its high specificity, MAGE-A3 has shown to be a promising candidate for cancer immunotherapy. Dendritic cells (DCs) have emerged as the natural agents for antigen delivery. DCs transduced with antigen may increase immune response and maintain immune durability. The aim of this study was to investigate the roles of DCs transduced with lentiviral vectors (LVs) encoding full-length MAGE-A3 gene in cancer immunotherapy .
  
  
  METHODS
  A LV containing full-length MAGE-A3 gene (rLV/MAGE-A3) was constructed. Reverse transcriptase-polymerase chain reaction and direct DNA sequencing were performed to verify the construct. Human DCs derived from umbilical cord blood were then transduced with rLV/MAGE-A3. The potency of rLV/MAGE-A3-transduced DCs was examined by measurement of surface markers and mixed lymphocyte reaction. The MAGE-A3-specific T-cell response induced by DCs was detected using the lactate dehydrogenase release assay.
  
  
  RESULTS
  rLV/MAGE-A3 was constructed successfully and used to transduce DCs efficiently. DCs transduced with rLV/MAGE-A3 stably expressed MAGE-A3 and yielded high percentage of cells expressing CD80, CD86, and HLA-DR. rLV/MAGE-A3 transduction did not impair DCs viability and maturation at a multiplicity of infection of 30. The rLV/MAGE-A3-transduced DCs induced MAGE-A3-specific T lymphocytes that exhibited a significant lysis activity against MAGE-A3-bearing tumor cell lines (HuH-7 and SGC-7901).
  
  
  CONCLUSIONS
  DC-directed rLV/MAGE-A3 efficiently induced antigen-specific immune responses, indicating the possibility of DC-based MAGE-A3 antigen vaccine as a promising strategy for treatment of MAGE-A3-associated cancer.
authors: Department of Pathology, Fujian Medical University, 88# Jiao Tong Road, Fuzhou, 350004, Fujian, People's Republic of China.
authors: Liyan
authors: L
authors: Lin
authors: Juanbing
authors: J
authors: Wei
authors: Yuqing
authors: Y
authors: Chen
authors: Aimin
authors: A
authors: Huang
authors: Kay Ka-Wai
authors: KK
authors: Li
authors: Wenmin
authors: W
authors: Zhang
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D022781:Hepatocytes / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D016086:Lentivirus / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger