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.
This work was supported by Grants from CaP CURE, the David H. Koch Charitable Foundation, The Ronald P. and Susan E. Lynch Foundation, the Lawrence and Carol Zicklin Philanthropic Fund, the William T. Morris Foundation, the John E. Wilson Research Fund, the Alissa Beth Bander Memorial Foundation, the Cornell Medical College Urological Oncology Research Fund, and BZL, Inc. N. H. B. is a consultant to BZL, Inc.; N. H. B.'s agreement with BZL is managed by Cornell University in accordance with its conflict of interest policies.