dendritic-based vaccine efficacy against HBV-related hepatocellular carcinoma

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Human Immunology
Volume 71, Issue 3, March 2010, Pages 255-262
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doi:10.1016/j.humimm.2009.12.010 | How to Cite or Link Using DOI
Copyright © 2010 American Society for Histocompatibility and Immunogenetics
Published by Elsevier Inc.

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


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Jing-Yue Yanga, Da-Yong Caob, Yan Xuea, Zhao-Cai Yua and Wen-Chao Liua, ,

a Department of Clinical Oncology, State Key Discipline of Cell Biology,
Xijing Hospital, Fourth Military Medical University, Xian, Shaanxi Province
710032, People's Republic of China
b Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military
Medical University, Xian, Shaanxi Province 710032, People's Republic of China

Received 1 August 2009;  accepted 17 December 2009.  Available online 8
January 2010.  Available online 8 January 2010.

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.