Cancer Immunology, Immunotherapy

, Volume 62, Issue 3, pp 585–596 | Cite as

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

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


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.


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



Androgen receptor


Ligand-binding domain


Moderately differentiated carcinoma


Poorly differentiated carcinoma


Prostatic intraepithelial neoplasia


Transgenic adenocarcinoma of the mouse prostate


Well-differentiated carcinoma



We thank Dr. François Lemonnier for provision of HHDII-DR1 animals (which are property of the Institut Pasteur, 25-28 rue de Docteur Roux, Paris, France 75015), and Drs. George Wilding and Ajit Verma for TRAMP+/+ mice. We also thank Drs. Ruth Sullivan and Weixiong Zhong for pathological consultations, Dr. Joan Jorgensen for help with immunofluorescence protocols, and Dr. Wei Huang and Sally Drew for assistance with the Vectra Imaging System. We would also like to thank Dr. Glenn Liu for critical evaluation of the manuscript. Grant support was provided by the National Institutes of Health (R01 CA142608, P30 CA014520), and by the US Army Medical Research and Materiel Command Prostate Cancer Research Program (W81XWH-05-1-0404, W81XWH-08-1-0341, and W81XWH-11-1-0196).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Supplementary material 1 (DOC 24 kb)
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Supplementary material 5 (TIFF 4687 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
    Email author
  1. 1.University of Wisconsin Carbone Cancer CenterMadisonUSA
  2. 2.7007 Wisconsin Institutes for Medical ResearchMadisonUSA

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