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Immunological Investigations
A Journal of Molecular and Cellular Immunology
Volume 42, 2013 - Issue 2
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Research Article

Improvement of HBsAg Gene-Modified Dendritic Cell-Based Vaccine Efficacy by Optimizing Immunization Method or the Application of β-glucosylceramide

, , , , , , , & show all
Pages 137-155 | Published online: 16 Jan 2013
 

Abstract

Hepatocellular carcinoma (HCC) in China is mostly Hepatitis B virus infection related. The antitumor efficacy of HBsAg gene-modified dendritic cells (DC) has been widely tested both in vitro and in vivo. In this study, we analyzed whether adenoviral vector mediated HBsAg expression would alter cell surface phenotype or autologous T cell stimulating function of mature DCs. Further, the anti-tumor efficacy of pAd-HBsAg-DC-based vaccine was evaluated in mice bearing HBsAg expressing HCC. We also tested whether β-glucosylceramide (β-GC) would enhance the anti-tumor activity of pAd-HBsAg-DC. Results revealed that pAd-HBsAg-DC expressed and secreted HBsAg, while maintaining phenotypic characteristics of mature DCs. Vaccination with pAd-HBsAg-DC conferred specific therapeutic antitumor immunity to animal model bearing HBsAg expressing HCC. The application of β-GC activated mice hepatic NKT cells and enhanced the antitumor activity of pAd-HBsAg-DC. Most importantly, in vivo results showed that the inhibiting effect of pAd-HBsAg-DC vaccination on tumor growth was more significant when applied before tumor inoculation, suggesting that genetically modified DC based therapeutic cancer vaccine may achieve the most optimized antitumor effect when applied before tumor onset, and β-GC may serve as a potent innate immune enhancer for augmenting the antitumor effect of pAd-HBsAg-DC vaccine.

ACKNOWLEDGMENT

We thank Dr. Chenghui Huang for kindly providing the recombinant adenoviral vector, pAd-HBsAg. This study was supported by the National Natural Science Foundation of China (No.30600156) and the Natural Science Foundation of Guangdong Province (No. 2011B031800022).

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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