title: The androgen receptor: a biologically relevant vaccine target for the treatment of prostate cancer.
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.
authors.affiliation: University of Wisconsin Carbone Cancer Center, 1111 Highland Avenue, Madison, WI 53705, USA. bmo@medicine.wisc.edu
authors.forename: Brian M
authors.initials: BM
authors.lastname: Olson
authors.forename: Laura E
authors.initials: LE
authors.lastname: Johnson
authors.forename: Douglas G
authors.initials: DG
authors.lastname: McNeel
mesh_terms: D000230:Adenocarcinoma / Q000517:prevention & control; D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D015789:HLA-A2 Antigen / Q000235:genetics; D015798:HLA-DR1 Antigen / Q000235:genetics; D006801:Humans; D007114:Immunization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000276:immunology / Q000401:mortality / Q000517:prevention & control / Q000628:therapy*; D017434:Protein Structure, Tertiary; D051381:Rats; D011944:Receptors, Androgen / Q000276:immunology*; D019444:Vaccines, DNA / Q000627:therapeutic use
chemical_list: C410798:AR protein, human; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D015798:HLA-DR1 Antigen; D011944:Receptors, Androgen; D019444:Vaccines, DNA