Cancer Immunology, Immunotherapy

, Volume 62, Issue 3, pp 585–596

The androgen receptor: a biologically relevant vaccine target for the treatment of prostate cancer

  • Brian M. Olson
  • Laura E. Johnson
  • Douglas G. McNeel
Original article

Abstract

The androgen receptor (AR) plays an essential role in the development and progression of prostate cancer. However, while it has long been the primary molecular target of metastatic prostate cancer therapies, it has not been explored as an immunotherapeutic target. In particular, the AR ligand-binding domain (LBD) is a potentially attractive target, as it has an identical sequence among humans as well as among multiple species, providing a logical candidate for preclinical evaluation. In this report, we evaluated the immune and anti-tumor efficacy of a DNA vaccine targeting the AR LBD (pTVG-AR) in relevant rodent preclinical models. We found immunization of HHDII-DR1 mice, which express human HLA-A2 and HLA-DR1, with pTVG-AR augmented AR LBD HLA-A2-restricted peptide-specific, cytotoxic immune responses in vivo that could lyse human prostate cancer cells. Using an HLA-A2-expressing autochthonous model of prostate cancer, immunization with pTVG-AR augmented HLA-A2-restricted immune responses that could lyse syngeneic prostate tumor cells and led to a decrease in tumor burden and an increase in overall survival of tumor-bearing animals. Finally, immunization decreased prostate tumor growth in Copenhagen rats that was associated with a Th1-type immune response. These data show that the AR is as a prostate cancer immunological target antigen and that a DNA vaccine targeting the AR LBD is an attractive candidate for clinical evaluation.

Keywords

Androgen receptor ligand-binding domain Prostate cancer vaccine HHDII-DR1 TRAMP T-cell immunity 

Abbreviations

AR

Androgen receptor

LBD

Ligand-binding domain

MDC

Moderately differentiated carcinoma

PDC

Poorly differentiated carcinoma

PIN

Prostatic intraepithelial neoplasia

TRAMP

Transgenic adenocarcinoma of the mouse prostate

WDC

Well-differentiated carcinoma

Supplementary material

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Supplementary material 1 (DOC 24 kb)
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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Brian M. Olson
    • 1
  • Laura E. Johnson
    • 1
  • Douglas G. McNeel
    • 1
    • 2
  1. 1.University of Wisconsin Carbone Cancer CenterMadisonUSA
  2. 2.7007 Wisconsin Institutes for Medical ResearchMadisonUSA

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