MONOCLONAL-ANTIBODIES TO THE EXTRACELLULAR DOMAIN OF PROSTATE-SPECIFIC MEMBRANE ANTIGEN ALSO REACT WITH TUMOR VASCULAR ENDOTHELIUM

Prostate-specific membrane antigen (PSMA), initially defined by monocl onal antibody (mAb) 7E11, is a now well-characterized type 2 integral membrane glycoprotein expressed in a highly restricted manner by prost ate epithelial cells. 7E11 has been shown to bind an intracellular epi tope of PSMA that, in viable cells, is not available for binding. Here in, we report the initial characterization of the first four reported IgG mAbs that bind the external domain of PSMA. Competitive binding st udies indicate these antibodies define two distinct. noncompeting epit opes on the extracellular domain of PSMA. In contrast to 7E11, these m Abs bind to viable LNCaP cells in vitro. In addition, they show strong immunohistochemical reactivity to tissue sections of prostate epithel ia, including prostate cancer. These mAbs were also strongly reactive with vascular endothelium within a wide variety of carcinomas (includi ng lung, colon, breast, and others) but not with normal vascular endot helium. These antibodies should prove useful for in vivo targeting to prostate cancer, as well as to the vascular compartment of a wide vari ety of carcinomas.