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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

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 cells Tumor antigens HBsAg CTL Adenoviral transduction 

Notes

Acknowledgements

This work was supported in part by grants from the Simeon M. Jones, Jr. and Katherine Reed Jones Fund, the Benjamin H. and Portia T. Hosler Fund, and the Walter P. Morrison, Jr. Family Fund administered through The Pittsburgh Foundation and in part by grant from NSFC (30200268)

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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

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