Improvement of dendritic-based vaccine efficacy against hepatitis B virus-related hepatocellular carcinoma by two tumor-associated antigen gene-infected dendritic cells.
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 alpha-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-gamma. 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.
Yang
Jing-Yue
JY
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.
Cao
Da-Yong
DY
Xue
Yan
Y
Yu
Zhao-Cai
ZC
Liu
Wen-Chao
WC
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005818:Genetic Engineering; D006680:HLA Antigens / Q000378:metabolism; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000235:genetics; D020014:K562 Cells; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D000509:alpha-Fetoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006680:HLA Antigens; D006514:Hepatitis B Surface Antigens; D053762:Interleukin-12 Subunit p40; D000509:alpha-Fetoproteins; D007371:Interferon-gamma