title: Three conformational antibodies specific for different PSMA epitopes are promising diagnostic and therapeutic tools for prostate cancer.
abstract: BACKGROUND
  The prostate specific membrane antigen (PSMA) represents an attractive antigen for antibody-based diagnostic and therapeutic intervention in prostate cancer, since it is highly restricted to the prostate and overexpressed in all tumor stages. The present work describes the in vitro characterization of the three anti-PSMA monoclonal antibodies (mAbs) 3/A12, 3/E7, and 3/F11 in comparison to the mAb J591.
  
  
  METHODS
  The mAbs were tested for saturation and competitive binding on C4-2 prostate cancer cells by flow cytometry. Immunohistochemical staining was conducted on frozen prostate normal and cancer tissues as well as on lymph node metastases. Similarly, potential crossreactivities were tested on a broad panel of human normal tissues.
  
  
  RESULTS
  The anti-PSMA mAbs showed a strong binding to C4-2 cells with mean half-maximal saturation concentrations of about 14 nM for 3/A12, 17 nM for 3/E7, 9 nM for 3/F11, and 16 nM for J591. Competitive binding studies revealed that our three mAbs bind to different extracellular PSMA epitopes. The mAbs showed comparable staining of epithelial cells for all tested normal and tumorous prostate tissues. Extraprostatic staining was observed on secretory cells of the salivary glands and on the brush border of the duodenal columnar epithelium. J591 additionally showed positive staining of the normal breast epithelium.
  
  
  CONCLUSIONS
  Due to their specific binding characteristics, the anti-PSMA mAbs 3/A12, 3/E7, and 3/F11 show great promise for diagnostic and therapeutic applications in prostate cancer.
authors: Department of Urology, Experimental Urology, University Hospital Freiburg, Freiburg, Germany. philipp.wolf@uniklinik-freiburg.de
authors: Philipp
authors: P
authors: Wolf
authors: Nikolaus
authors: N
authors: Freudenberg
authors: Patrick
authors: P
authors: Bühler
authors: Karen
authors: K
authors: Alt
authors: Wolfgang
authors: W
authors: Schultze-Seemann
authors: Ulrich
authors: U
authors: Wetterauer
authors: Ursula
authors: U
authors: Elsässer-Beile
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000276:immunology*; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D000939:Epitopes; D043425:Glutamate Carboxypeptidase II / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011467:Prostate / Q000276:immunology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II