Diverse efficacy of vaccination therapy using the alpha-fetoprotein gene against mouse hepatocellular carcinoma.
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.
Saeki
Akira
A
First Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Nakao
Kazuhiko
K
Nagayama
Yuji
Y
Yanagi
Kenji
K
Matsumoto
Kojiro
K
Hayashi
Toshinobu
T
Ishikawa
Hiroki
H
Hamasaki
Keisuke
K
Ishii
Nobuko
N
Eguchi
Katsumi
K
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
D019496:Cancer Vaccines; D019444:Vaccines, DNA; D000509:alpha-Fetoproteins; D007371:Interferon-gamma