title: alpha-Fetoprotein-specific tumor immunity induced by plasmid prime-adenovirus boost genetic vaccination.
abstract: alpha-Fetoprotein (AFP) is a potential target for immunotherapy in hepatocellular carcinoma; both the murine and human T-cell repertoires can recognize AFP-derived epitopes in the context of the MHC. Protective immunity can be generated with AFP-engineered dendritic cell-based vaccines. We now report a DNA-based immunization strategy using a prime-boost approach: coadministration of plasmid DNA encoding murine AFP and murine granulocyte-macrophage colony-stimulating factor followed by boosting with an AFP-expressing nonreplicating adenoviral vector. This immunization strategy can elicit a high frequency of Th1-type AFP-specific cells leading to tumor protective immunity in mice at levels comparable with AFP-engineered dendritic cells. This cell-free mode of immunization is better suited for large-scale vaccine efforts for patients with hepatocellular carcinoma.
authors.affiliation: Division of Surgical Oncology, [University of California, Los Angeles, Los Angeles, California 90095, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Meng
authors.forename: L H
authors.initials: LH
authors.lastname: Butterfield
authors.forename: A
authors.initials: A
authors.lastname: Ribas
authors.forename: V B
authors.initials: VB
authors.lastname: Dissette
authors.forename: J B
authors.initials: JB
authors.lastname: Heller
authors.forename: G A
authors.initials: GA
authors.lastname: Miranda
authors.forename: J A
authors.initials: JA
authors.lastname: Glaspy
authors.forename: W H
authors.initials: WH
authors.lastname: McBride
authors.forename: J S
authors.initials: JS
authors.lastname: Economou
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D016233:Immunotherapy, Active / Q000379:methods; D019169:Jurkat Cells / Q000276:immunology / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D019444:Vaccines, DNA; D000509:alpha-Fetoproteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor