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A new generation of monoclonal and recombinant antibodies against cell‐adherent prostate specific membrane antigen for diagnostic and therapeutic targeting of prostate cancer
Author(s) -
ElsässerBeile Ursula,
Wolf Philipp,
Gierschner Dorothee,
Bühler Patrick,
SchultzeSeemann Wolfgang,
Wetterauer Ulrich
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20367
Subject(s) - lncap , glutamate carboxypeptidase ii , monoclonal antibody , prostate cancer , antibody , antigen , cancer research , epitope , microbiology and biotechnology , transfection , prostate , medicine , cancer , cell culture , immunology , biology , genetics
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. Prostate 66: 1359–1370, 2006. © 2006 Wiley‐Liss, Inc.