Improvement of dendritic-based vaccine efficacy against hepatitis B virus–related hepatocellular carcinoma by two tumor-associated antigen gene–infected dendritic cells

Abstract

Recently, studies on dendritic cell (DC) vaccine have focused on the development of more effective DC vaccine regimen, such as the application of multiple tumor-associated antigen–targeted DC vaccine. This approach could be used to enhance efficacy of DC-based vaccine against tumors and infectious diseases. In this study, we analyzed whether DC from patients with hepatocellular carcinoma can be infected with the α-fetoprotein (AFP) gene and/or HBsAg gene (hepatocellular carcinoma–related antigen). Further, it was examined whether vaccination using these genetically engineered DC can induce stronger therapeutic antitumor immunity. Results revealed that DC infected with AdAFP (adenovirus AFP)/HBsAg can express AFP and HBsAg by reverse transcription–polymerase chain reaction and Western blot techniques. Compared with those before transfection, the expressions of membrane molecules increased dramatically. Specific T cells generated by DCs infected with AdAFP/HBsAg specifically recognized human leukocyte antigen–matched HepG2.2.15 cell lines. Moreover, the cytotoxic activity of cytotoxic T lymphocytes against HepG2.2.15 with DCs expressing AFP was significantly augmented by coinfection with the HBsAg gene. Administration with such vaccine also significantly increased the production of interleukin-12p70 and interferon-γ. Most importantly, in vivo results suggested that inhibitors of tumor growth were most significant in severe combined immunodeficiency mice model, which was treated with induced cytotoxic T lymphocyte by the AFP/HBsAg-DC vaccine. These results indicate that a vaccination therapy using DCs coinfected with the two tumor-associated antigen genes is an effective strategy for immunotherapy in the activation of DCs, CD4+ T cells, and CD8+ T cells, and may be useful in the clinical application of cancer vaccine therapy.