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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

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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.

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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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Authors and Affiliations

  1. , Suite 200, 750 Welch Road, Palo Alto, CA, 94304 , USA

    C. Andrew Bonham

  2. Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa., USA

    Shuang-Jian Qiu, Lina Lu, LiangFu Wang, Shiguang Qian, John J. Fung, C. Andrew Bonham & C. Andrew Bonham

  3. Department of Surgery and Department of Molecular Genetics & Biochemistry, University of Pittsburgh Medical Center, Pittsburgh, Pa., USA

    Chunping Qiao, LiangFu Wang, Zhong Wang & Xiao Xiao

  4. Liver Cancer Institute and Zhongshan Hospital, Fudan University, 200032, Shanghai, China

    Shuang-Jian Qiu & Sheng-Long Ye

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  1. Shuang-Jian Qiu
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  2. Lina Lu
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Correspondence to C. Andrew Bonham.

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Qiu, SJ., Lu, L., Qiao, C. et al. Induction of tumor immunity and cytotoxic t lymphocyte responses using dendritic cells transduced by adenoviral vectors encoding HBsAg: comparison to protein immunization. J Cancer Res Clin Oncol 131, 429–438 (2005). https://doi.org/10.1007/s00432-004-0616-1

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  • DOI: https://doi.org/10.1007/s00432-004-0616-1

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