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TGF-β insensitive dendritic cells: an efficient vaccine for murine prostate cancer

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Abstract

Dendritic cells (DCs) are highly potent initiators of the immune response, but DC effector functions are often inhibited by immunosuppressants such as transforming growth factor beta (TGF-β). The present study was conducted to develop a treatment strategy for prostate cancer using a TGF-β-insensitive DC vaccine. Tumor lysate-pulsed DCs were rendered TGF-β insensitive by dominant-negative TGF-β type II receptor (TβRIIDN), leading to the blockade of TGF-β signals to members of the Smad family, which are the principal cytoplasmic intermediates involved in the transduction of signals from TGF-β receptors to the nucleus. Expression of TβRIIDN did not affect the phenotype of transduced DCs. Phosphorylated Smad-2 was undetectable and expression of surface co-stimulatory molecules (CD80/CD86) were upregulated in TβRIIDN DCs after antigen and TGF-β1 stimulation. Vaccination of C57BL/6 tumor-bearing mice with the TβRIIDN DC vaccine induced potent tumor-specific cytotoxic T lymphocyte responses against TRAMP-C2 tumors, increased serum IFN-γ and IL-12 level, inhibited tumor growth and increased mouse survival. Furthermore, complete tumor regression occurred in two vaccinated mice. These results demonstrate that blocking TGF-β signals in DC enhances the efficacy of DC-based vaccines.

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Acknowledgment

This study was supported in part by grants from the Nature Science Foundation of China (Project No. 30471738 and 30300413) and the Technology Plan Emphasis Item of Peking (Project No. D0206011000091). We are grateful to the NIH Fellows Editorial Board for their editorial assistance.

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Authors and Affiliations

  1. Department of Urology, ****g Hospital, Fourth Military Medical University, 15 Chang Le West Road, **’an, Shaanxi, 710032, China

    Fu-Li Wang, Feng Tian, Bin Song & He Wang

  2. Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, Bei**g, 100043, China

    Wei-Jun Qin & Ying-Lu Guo

  3. Department of Immunology, Fourth Military Medical University, 17 Chang Le West Road, **’an, 710032, China

    Wei-Hong Wen

  4. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Qiang Zhang & Chung Lee

  5. Department of Urology, the First People’s Hospital of Guangzhou, Guangzhou, 510180, China

    Wei-de Zhong

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  1. Fu-Li Wang
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Correspondence to He Wang.

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Fu-Li Wang, Wei-Jun Qin contributed equally to this report.

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Wang, FL., Qin, WJ., Wen, WH. et al. TGF-β insensitive dendritic cells: an efficient vaccine for murine prostate cancer. Cancer Immunol Immunother 56, 1785–1793 (2007). https://doi.org/10.1007/s00262-007-0322-3

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  • DOI: https://doi.org/10.1007/s00262-007-0322-3

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