Department of Urology, Experimental Urology, University Hospital Freiburg, Freiburg, Germany.
Prostate. 2010 Apr 1;70(5):562-9. doi: 10.1002/pros.21090.
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.
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.
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.
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.
前列腺特异性膜抗原（PSMA）是一种很有吸引力的抗原，可用于前列腺癌的抗体诊断和治疗干预，因为它高度局限于前列腺，并且在所有肿瘤阶段都过度表达。本研究描述了三种抗 PSMA 单克隆抗体（mAb）3/A12、3/E7 和 3/F11 与 mAb J591 的体外特性。
通过流式细胞术检测 mAb 在 C4-2 前列腺癌细胞上的饱和和竞争结合。对冷冻的前列腺正常和癌组织以及淋巴结转移进行免疫组织化学染色。同样，在广泛的人类正常组织面板上测试了潜在的交叉反应性。
抗 PSMA mAb 与 C4-2 细胞具有很强的结合力，3/A12 的平均半最大饱和浓度约为 14 nM，3/E7 为 17 nM，3/F11 为 9 nM，J591 为 16 nM。竞争结合研究表明，我们的三种 mAb 结合到不同的 PSMA 细胞外表位。mAb 对所有测试的正常和肿瘤前列腺组织的上皮细胞均显示出相似的染色。在外分泌细胞的唾液腺和十二指肠柱状上皮的刷状缘上观察到额外的前列腺外染色。J591 还对正常乳腺上皮显示出阳性染色。
由于其特异性结合特性，抗 PSMA mAb 3/A12、3/E7 和 3/F11 有望在前列腺癌的诊断和治疗应用中具有很大的潜力。
