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

Fu Li Wang, Wei Jun Qin, Wei Hong Wen, Feng Tian, Bin Song, Qiang Zhang, Chung Lee, Wei De Zhong, Ying Lu Guo, He Wang*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1785-1793
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume56
Issue number11
DOIs
StatePublished - Nov 1 2007

Keywords

  • Dendritic cell
  • Immuno-gene therapy
  • Prostate cancer
  • Receptor
  • TGF-β
  • Vaccination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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  • Cite this

    Wang, F. L., Qin, W. J., Wen, W. H., Tian, F., Song, B., Zhang, Q., Lee, C., Zhong, W. D., Guo, Y. L., & Wang, H. (2007). TGF-β insensitive dendritic cells: An efficient vaccine for murine prostate cancer. Cancer Immunology, Immunotherapy, 56(11), 1785-1793. https://doi.org/10.1007/s00262-007-0322-3