PSMA specific antibodies and their diagnostic and therapeutic use

Abstract

Prostate-specific membrane antigen (PSMA) is a membrane-bound glycoprotein highly restricted to prostatic epithelial cells. PSMA expression is increased in association with prostatic cancer, particularly in hormone refractory disease. Given its membrane-bound character, PSMA is an ideal sentinel molecule for use in targeting prostatic cancer cells. Monoclonal antibodies specific for PSMA are available, beginning with the antibody 7E11.C5 which originally defined PSMA and which has been developed for use in cancer detection via immunoscintiscanning in the ProstaScint test. Newer second generation antibodies specific for both linear amino acid sequence epitopes and protein conformational epitopes on the extracellular domain of PSMA have been reported. Although most of these are murine antibodies, both humanised and fully human examples have been developed. These antibodies are beginning to work their way into clinical applications for potential improved diagnostic and therapeutic uses. Results to date suggest that antibodies specific for extracellular epitopes are significantly better for clinical uses in vivo than the 7E11.C5 antibody that is specific for an intracellular epitope. Current knowledge relating to PSMA-specific antibodies and their clinical uses and potential is described and evaluated.