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[800] Novel Anti-PSMA Monoclonal Antibodies Show Superior Tissue Specificity
K Sircar, N Bernard, AC Cuello, HU Saragovi, P Gold, AG Aprikian, S Moffett. McGill University, Montreal, QC, Canada; ProScan Rx Pharma, Montreal, QC, Canada
Background: PSMA, a type II membrane protein expressed on prostatic acinar cells, is a potentially attractive target for prostate cancer diagnostics and therapeutics. We have generated novel murine monoclonal antibodies(mAb) against a specific extracellular peptide epitope of PSMA and tested their tissue reactivity by immunohistochemistry. Design: We have used mAbs called 17G1 and 20F2 to screen tissue microarrays of 22 different normal tissues and 19 different tumor types in order to characterize their recognition specificity. The immunohistochemistry was performed on antigen retrieved, formalin fixed, paraffin embedded material. Anti-PSMA mAbs J591 and 7E11 were used as reference standards. Results: 17G1 and 20F2 both showed the expected immunoreactivity to the apical surface of prostatic acinar cells in benign, premalignant and malignant prostatic tissues. Similar to J591, staining of cancer sections was more intense than benign.
Anti-PSMA tissue specificity| Tissue | J591 | 17G1 | 20F2 | | Skeletal muscle | + | + | - | | Small bowel | weak | + | + | | Kidney tubules | + | + | - |
Nonreactive normal tissues included fat, bladder, brain, colon, esophagus, gallbladder, heart, liver, lung, pancreas, rectum, skin, spleen, stomach, testis, thymus, thyroid, tonsil.
Anti-PSMA tumor specificity| Tumor | J591 | 17G1 | 20F2 | 7E11 | | Rhabdomyosarcoma | - | + | - | + | | Melanoma | - | + | - | + | | Thyroid Carcinoma | - | - | - | + | | Gastric Carcinoma | - | + | - | weak |
Nonreactive tumors included astrocytoma, carcinoid, colon Ca, epithelioid sarcoma, Ewings sarcoma,, hepatocellular Ca, Hodgkin s and non-Hodgkin s lymphoma, lung Ca, leiomyoma, MFH, mesothelioma, pancreatic Ca, renal Ca. Conclusions: Our study demonstrates that anti-PSMA mAb 20F2 shows superior tissue specificity compared to J591. While maintaining prostate tumor specificity, it did not recognize kidney or skeletal muscle which were stained by J591 and 17G1. Category: Genitourinary (including renal tumors)
Wednesday, March 28, 2007
Poster # 93, Wednesday Morning
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