Three conformational antibodies specific for different PSMA epitopes are promising diagnostic and therapeutic tools for prostate cancer

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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. Prostate 70: 562–569, 2010.
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  • Deutsche Krebshilfe

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