Transforming growth factor β inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines

James J. Kobie, Rita S. Wu, Robert A. Kurt, Sunming Lou, Miranda K. Adelman, Luke J. Whitesell, Lalitha V. Ramanathapuram, Carlos L. Arteaga, Emmanuel T. Akporiaye

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197 Scopus citations

Abstract

Dendritic cell (DC)-based vaccines have exhibited minimal effectiveness in treating established tumors, likely because of factors present in the tumor microenvironment. One such factor is transforming growth factor β (TGF-β), a cytokine that is produced by numerous tumor types and has been demonstrated to impair DC functions in vitro. We have evaluated the effect of TGF-β on the immunostimulatory activities of DCs. We demonstrate that TGF-β exposure inhibits the ability of DCs to present antigen, stimulate tumor-sensitized T lymphocytes, and migrate to draining lymph nodes. Neutralization of TGF-β using the TGF-β-neutralizing monoclonal antibody 2G7 enhanced the ability of DC vaccines to inhibit the growth of established 4T1 murine mammary tumors. Treatment of 4T1 tumors transduced with the antisense TGF-β transgene (4T1-asT) with the combination of DC and 2G7 monoclonal antibody inhibited tumor growth and resulted in complete regression of tumors in 40% of the mice. These results demonstrate that neutralization of TGF-β in tumor-bearing mice enhances the efficacy of DC-based vaccines.

Original languageEnglish (US)
Pages (from-to)1860-1864
Number of pages5
JournalCancer research
Volume63
Issue number8
StatePublished - Apr 15 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kobie, J. J., Wu, R. S., Kurt, R. A., Lou, S., Adelman, M. K., Whitesell, L. J., Ramanathapuram, L. V., Arteaga, C. L., & Akporiaye, E. T. (2003). Transforming growth factor β inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines. Cancer research, 63(8), 1860-1864.