title: Diverse efficacy of vaccination therapy using the alpha-fetoprotein gene against mouse hepatocellular carcinoma.
abstract: Antitumor vaccination therapy approaches using naked plasmid DNA or recombinant viruses encoding tumor-associated antigens are currently in development. In the present study, we examined the therapeutic efficacy of vaccination using the mouse alpha-fetoprotein (AFP) gene in mouse hepatocellular carcinoma (HCC) cells. C57L/J or C3H/HeN mice were primed with an injection of naked plasmid DNA expressing mouse AFP followed by a booster of replication-defective adenovirus expressing mouse AFP (plasmid-AFP prime/adenovirus-AFP booster vaccination). The mice were then challenged with high AFP-producing Hepa1-6 cells or low AFP-producing MH134 cells, respectively, and the tumor growth rate was monitored. Plasmid-AFP prime/adenovirus-AFP booster vaccination promoted protective immunity against Hepa1-6 cells, and significantly increased the number of interferon-gamma-producing splenic cells in C57L/J mice. In addition, this vaccination protocol repressed the growth of pre-established Hepa1-6 tumors in C57L/J mice. However, plasmid-AFP prime/adenovirus-AFP booster vaccination did not induce protective immunity against MH134 cells in C3H/HeN mice. These results suggest that vaccination with the AFP gene is a promising strategy to treat HCC, but its outcome may be affected by the level of AFP expression in HCC or by the immunological response of the host.
authors.affiliation: First Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Saeki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakao
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagayama
authors.forename: Kenji
authors.initials: K
authors.lastname: Yanagi
authors.forename: Kojiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Hayashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hamasaki
authors.forename: Nobuko
authors.initials: N
authors.lastname: Ishii
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D000256:Adenoviridae; D000818:Animals; D019496:Cancer Vaccines / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000187:drug effects; D051379:Mice; D010957:Plasmids / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects; D019444:Vaccines, DNA / Q000494:pharmacology*; D000509:alpha-Fetoproteins / Q000235:genetics* / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D019444:Vaccines, DNA; D000509:alpha-Fetoproteins; D007371:Interferon-gamma