Search

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. [Copyright &y& Elsevier]

Abstract: The T-helper 1 (Th1) immune reaction is most important in dendritic cell (DC)–based immunotherapy. Interleukin (IL)–18, a Th1-biasing cytokine, plays a pivotal role in inducing cytotoxic T lymphocyte (CTL) responses. In this study, we analyzed whether dendritic cells (DCs) from patients with hepatocellular carcinoma (HCC) can be transduced with the IL-18 gene and/or α-fetoprotein (AFP) gene, and we examined whether vaccinations using these genetically engineered DC can induce stronger therapeutic antitumor immunity. The results showed that DC transfected with AdIL-18/AFP can expressed IL-18 and AFP by reverse transcriptase–polymerase chain reaction and enzyme-linked immunoassay. Compared with those before transfection, the expressions of membrane molecules were increased dramatically. Specific T cells generated by DC transfected with AdIL-18/AFP recognized HLA-matched HepG2 cell lines specifically. Most importantly, The cytotoxic activity of CTLs against HepG2 with DC expressing AFP(AFP-DC) was significantly augmented by co-transduction with the IL-18 gene. Administration with such vaccine also significantly increased the production of interleukin-12p70 and interferon-γ. These results indicate that a vaccination therapy using DC co-transduced with the TAA gene and IL-18 genes is effective strategy for immunotherapy in terms of the activation of DCs, CD4+ T, cells and CD8+ T cells, and may be useful in the clinical application of a cancer vaccine therapy. [Copyright &y& Elsevier]