Induction of tumor immunity and cytotoxic t lymphocyte responses using dendritic cells transduced by adenoviral vectors encoding HBsAg: comparison to protein immunization

  • Shuang-Jian Qiu
  • Lina Lu
  • Chunping Qiao
  • LiangFu Wang
  • Zhong Wang
  • Xiao Xiao
  • Shiguang Qian
  • John J. Fung
  • Sheng-Long Ye
  • C. Andrew Bonham
Original Paper

DOI: 10.1007/s00432-004-0616-1

Cite this article as:
Qiu, SJ., Lu, L., Qiao, C. et al. J Cancer Res Clin Oncol (2005) 131: 429. doi:10.1007/s00432-004-0616-1

Abstract

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.

Keywords

Dendritic cellsTumor antigensHBsAgCTLAdenoviral transduction

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Shuang-Jian Qiu
    • 2
    • 4
  • Lina Lu
    • 2
  • Chunping Qiao
    • 3
  • LiangFu Wang
    • 2
    • 3
  • Zhong Wang
    • 3
  • Xiao Xiao
    • 3
  • Shiguang Qian
    • 2
  • John J. Fung
    • 2
  • Sheng-Long Ye
    • 4
  • C. Andrew Bonham
    • 1
    • 2
    • 2
  1. 1.Palo AltoUSA
  2. 2.Thomas E. Starzl Transplantation InstituteUniversity of Pittsburgh Medical CenterPittsburghUSA
  3. 3.Department of Surgery and Department of Molecular Genetics & BiochemistryUniversity of Pittsburgh Medical CenterPittsburghUSA
  4. 4.Liver Cancer Institute and Zhongshan HospitalFudan UniversityShanghaiChina