title: Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium.
abstract: Prostate-specific membrane antigen (PSMA), initially defined by monoclonal antibody (mAb) 7E11, is a now well-characterized type 2 integral membrane glycoprotein expressed in a highly restricted manner by prostate epithelial cells. 7E11 has been shown to bind an intracellular epitope of PSMA that, in viable cells, is not available for binding. Herein, we report the initial characterization of the first four reported IgG mAbs that bind the external domain of PSMA. Competitive binding studies indicate these antibodies define two distinct, noncompeting epitopes on the extracellular domain of PSMA. In contrast to 7E11, these mAbs bind to viable LNCaP cells in vitro. In addition, they show strong immunohistochemical reactivity to tissue sections of prostate epithelia, including prostate cancer. These mAbs were also strongly reactive with vascular endothelium within a wide variety of carcinomas (including lung, colon, breast, and others) but not with normal vascular endothelium. These antibodies should prove useful for in vivo targeting to prostate cancer, as well as to the vascular compartment of a wide variety of carcinomas.
authors.affiliation: Department of Urology, New York Hospital-Cornell Medical Center, New York, New York 10021, USA.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: P
authors.initials: P
authors.lastname: Moy
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.forename: A
authors.initials: A
authors.lastname: Rajasekaran
authors.forename: V
authors.initials: V
authors.lastname: Navarro
authors.forename: B
authors.initials: B
authors.lastname: Knudsen
authors.forename: N H
authors.initials: NH
authors.lastname: Bander
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology*; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology*; D001667:Binding, Competitive; D015153:Blotting, Western; D003429:Cross Reactions; D004730:Endothelium, Vascular / Q000276:immunology; D019084:Fluorescent Antibody Technique, Indirect; D043425:Glutamate Carboxypeptidase II; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D007074:Immunoglobulin G; D043425:Glutamate Carboxypeptidase II