Induction of tumor immunity and cytotoxic t lymphocyte responses using dendritic cells transduced by adenoviral vectors encoding HBsAg: comparison to protein immunization.
Dendritic cells (DC) are specialized antigen-presenting cells with powerful immunostimulatory properties. Their use for induction of anti-tumor immunity has been limited by several factors, including identification of appropriate tumor-associated antigens, delivery of antigens to DC, and maintaining DC in a highly activated state. Here, DC propagated in vitro were transduced with an adenoviral (Ad) vector to express hepatitis B surface antigen (HBsAg), an antigen present in hepatocellular carcinoma (HCC). Many patients with HCC demonstrate evidence of prior HBV exposure, suggesting that the presence of the virus in a quiescent state may promote tumorigenesis. Ad-HBsAg-transduced DC stimulated strong cytotoxic T lymphocyte (CTL) responses to HBsAg-expressing tumor cells, and protected mice from lethal tumor challenge. Immunity was antigen-specific, as wild-type tumor (HBsAg -) grew normally. Furthermore, DC transduced with an irrelevant vector had no effect. Vaccination with HBsAg protein, a clinically utilized preparation that confers immunity to HBV infection, did not protect against tumor challenge even though it induced a strong antibody response. These studies describe for the first time the contributions of humoral and cellular immune responses to tumor immunity induced by Ad-transduced DC compared to protein vaccination.
Qiu
Shuang-Jian
SJ
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Lu
Lina
L
Qiao
Chunping
C
Wang
LiangFu
L
Wang
Zhong
Z
Xiao
Xiao
X
Qian
Shiguang
S
Fung
John J
JJ
Ye
Sheng-Long
SL
Bonham
C Andrew
CA
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D005822:Genetic Vectors; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007114:Immunization; D007167:Immunotherapy; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006514:Hepatitis B Surface Antigens