title: In vivo effects of vaccination with six-transmembrane epithelial antigen of the prostate: a candidate antigen for treating prostate cancer.
abstract: Immunotherapy may provide an alternative treatment for cancer patients, especially when tumors overexpress antigens that can be recognized by immune cells. The identification of markers and therapeutic targets that are up-regulated in prostate cancer has been important to design new potential treatments for prostate cancer. Among them, the recently identified six-transmembrane epithelial antigen of the prostate (STEAP) is considered attractive due to its overexpression in human prostate cancer tissues. Our study constitutes the first assessment of the in vivo effectiveness of STEAP-based vaccination in prophylactic and therapeutic mouse models. Two delivery systems, cDNA delivered by gene gun and Venezuelan equine encephalitis virus-like replicon particles (VRP), both encoding mouse STEAP (mSTEAP) and three vaccination strategies were used. Our results show that mSTEAP-based vaccination was able to induce a specific CD8 T-cell response against a newly defined mSTEAP epitope that prolonged the overall survival rate in tumor-challenged mice very significantly. This was achieved without any development of autoimmunity. Surprisingly, CD4 T cells that produced IFNgamma, tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2) played the main role in tumor rejection in our model as shown by using CD4- and CD8-deficient mice. In addition, the presence of high IL-12 levels in the tumor environment was associated with a favorable antitumor response. Finally, the therapeutic effect of STEAP vaccination was also assessed and induced a modest but significant delay in growth of established, 31 day old tumors. Taken together, our data suggest that vaccination against mSTEAP is a viable option to delay tumor growth.
authors.affiliation: Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Los Angeles, California, USA.
authors.forename: Maria de la Luz
authors.initials: Mde L
authors.lastname: Garcia-Hernandez
authors.forename: Andrew
authors.initials: A
authors.lastname: Gray
authors.forename: Bolyn
authors.initials: B
authors.lastname: Hubby
authors.forename: W Martin
authors.initials: WM
authors.lastname: Kast
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology / Q000627:therapeutic use; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D048708:Cell Growth Processes / Q000276:immunology; D004277:DNA, Single-Stranded / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D012217:Rheumatoid Factor / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D001324:Autoantigens; D019496:Cancer Vaccines; D004277:DNA, Single-Stranded; C486624:Steap protein, mouse; D019444:Vaccines, DNA; D012217:Rheumatoid Factor