title: A new generation of monoclonal and recombinant antibodies against cell-adherent prostate specific membrane antigen for diagnostic and therapeutic targeting of prostate cancer.
abstract: BACKGROUND
  Prostate-specific membrane antigen (PSMA) is an excellent candidate for targeting prostate cancer by virtue of its restricted expression on prostatic epithelial cells and its upregulation on prostatic carcinoma cells. PSMA is expressed on the cell surface displaying a specific three-dimensional structure. Therefore, only antibodies with a high cell binding activity will have an important impact on antibody-based imaging and therapy.
  
  
  METHODS
  Monoclonal antibodies (mAbs) and single chain antibody fragments (scFvs) were prepared from spleen cells of mice that had been immunized either with purified PSMA or a cell lysate of prostate cancer LNCaP cells containing native PSMA. mAbs and scFvs were screened for reactivity with purified PSMA and binding to PSMA-expressing LNCaP cells.
  
  
  RESULTS
  From mice immunized with purified PSMA, we obtained three mAbs (K7, K12, D20) and four scFvs (G0, G1, G2, G4), which were highly reactive with the isolated antigen, but showed weak or no reaction with viable LNCaP cells. From mice immunized with unpurified LNCaP lysate, we obtained three mAbs (3/E7, 3/F11, 3/A12), and one scFv (A5), which were reactive with purified PSMA, also showing a strong and specific binding to viable LNCaP cells and PSMA-transfected cells.
  
  
  CONCLUSIONS
  Our results suggest that only the mAbs and scFvs, that were elicited with unpurified LNCaP lysate and not with purified PSMA will be useful agents for diagnostic imaging and therapeutic applications of prostate cancer.
authors.affiliation: Department of Urology, Experimental Urology, University of Freiburg, Freiburg, Germany. ursula.elsaesser@uniklinik-freiburg.de
authors.forename: Ursula
authors.initials: U
authors.lastname: Elsässer-Beile
authors.forename: Philipp
authors.initials: P
authors.lastname: Wolf
authors.forename: Dorothee
authors.initials: D
authors.lastname: Gierschner
authors.forename: Patrick
authors.initials: P
authors.lastname: Bühler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schultze-Seemann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wetterauer
mesh_terms: D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000276:immunology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D043425:Glutamate Carboxypeptidase II / Q000276:immunology*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D008297:Male; D017430:Prostate-Specific Antigen / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D012680:Sensitivity and Specificity
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007128:Immunoglobulin Fragments; D011994:Recombinant Proteins; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen