T lymphocyte responses against hepatitis B virus-related hepatocellular carcinoma induced by adenovirus vaccine encoding HBx.
HBx is an oncogenic tumor-associated antigen and is dominantly expressed in hepatitis and hepatoma tissues, the induction of active cellular responses against HBx should be a promising approach for the treatment of hepatitis B virus-related hepatocellular carcinoma. The present study was designed to test whether a replication-defective adenovirus vaccine expressing HBx antigen could be effectively used in the immunotherapy of hepatocellular carcinoma. To validate the possibility, we developed a novel HBx-positive hepatocellular carcinoma in mice by inoculated the pcDNA-HBx transfected Hepa1-6 cells subcutaneously into the right flank of mice. We found that immunotherapy with Ad-HBx was effective at both protective and therapeutic antitumor immunity in the hepatoma models in immune-competent mice. Histological examination revealed that Ad-HBx treatment led to significantly increased induction of apoptosis, tumor necrosis, and elevated CD8+ lymphocyte infiltration. In addition, the induction efficacy of the CTL response is dramatically enhanced by immunotherapy. Cytokine analysis confirmed that the antitumor efficacy of Ad-HBx may mostly result from cellular immunity. Our findings may prove useful in development of adenovirus vaccine based on HBx antigen to the treatment of HBV-associated hepatocellular carcinoma.
State Key Laboratory of Biotherapy, West China Hospital and College of Life Science, Sichuan University, #1 Keyuan Street 4, Gaopeng Street, Chengdu, P.R. China.
Yuhua
Y
Li
Ping
P
Cheng
Yanjun
Y
Wen
Ping
P
Chen
Li
L
Yang
Xia
X
Zhao
Huimin
H
Lv
Qingli
Q
Quan
Yonglin
Y
Wu
Huiqiang
H
Yang
Jie
J
Liu
Xueru
X
Wen
Nina
N
Liu
Zhuang
Z
Kang
Shan
S
Luo
Lian
L
Wang
Yuquan
Y
Wei
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D057809:HEK293 Cells; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008114:Liver Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy / Q000821:virology; D051379:Mice; D008856:Microscopy, Fluorescence; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
D019496:Cancer Vaccines; D016207:Cytokines; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein