title: Identification of AKAP-4 as a new cancer/testis antigen for detection and immunotherapy of prostate cancer.
abstract: BACKGROUND
  Prostate cancer (PC) is the second most common cancer in older men, after skin cancer. PC is difficult to diagnose because the prostate-specific antigen screening method is associated with many false positives. In addition there is a need to develop new and more effective treatments. Among presently available new treatments, immunotherapy is a promising approach. We investigated the expression of the cancer/testis antigen, AKAP-4, in PC patients to evaluate the possibility of exploiting AKAP-4 as a target for immunotherapy.
  
  
  METHODS
  We analyzed normal prostate tissues, 15 patients with PC and the LnCAP PC cell line by immunohistochemistry. We tested AKAP-4 immunogenicity through indirect ELISA on sera from patients and healthy subjects, and we generated in vitro AKAP-4-specific cytotoxic lymphocytes from peripheral blood mononuclear cells.
  
  
  RESULTS
  AKAP-4 was shown both at the cytoplasmic and surface levels of the LnCAP PC cell line. AKAP-4 was also highly expressed in PC cells from patients. We detected specific anti-AKAP-4 circulating immunoglobulins in AKAP-4 positive subjects. Using recombinant AKAP-4 loaded autologous dendritic cells, we generated AKAP-4-specific and HLA-I-restricted cytotoxic T lymphocytes able to kill PC cells in vitro. Further characterization indicated a Th-1 skewing in the cytokine secretion profile of these cells.
  
  
  CONCLUSIONS
  We demonstrate the aberrant expression of AKAP-4 in PC, which will potentially be developed as a biomarker in PC. We provide evidence that AKAP-4 is a potential target for PC adoptive immunotherapy or anti-tumor vaccination.
authors.affiliation: Division of Hematology & Oncology, Texas Tech University Health Sciences Center and The Southwest Cancer Treatment and Research Center, Lubbock, Texas 79430, USA. maurizio.chiriva@ttuhsc.edu
authors.forename: Maurizio
authors.initials: M
authors.lastname: Chiriva-Internati
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Yu
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mirandola
authors.forename: Nicholas
authors.initials: N
authors.lastname: D'Cunha
authors.forename: Fred
authors.initials: F
authors.lastname: Hardwicke
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Cannon
authors.forename: Everardo
authors.initials: E
authors.lastname: Cobos
authors.forename: W Martin
authors.initials: WM
authors.lastname: Kast
mesh_terms: D054758:A Kinase Anchor Proteins / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D007167:Immunotherapy; D008297:Male; D011467:Prostate / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D013737:Testis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D054758:A Kinase Anchor Proteins; C485480:AKAP4 protein, human; D017430:Prostate-Specific Antigen