Antibody-drug conjugates targeting prostate-specific membrane antigen

Abstract

Prostate-specific membrane antigen (PSMA) is an integral, non-shed membrane glycoprotein that is a well-characterized and clinically validated marker of prostate cancer. The expression profile and other biological properties of PSMA make it an attractive target for antibody-drug conjugate (ADC) therapy of prostate cancer, as well as a broad range of other tumors in which PSMA is abundantly expressed within the tumor neovasculature. PSMA-targeted ADCs have been developed using auristatin and maytansinoid drugs, and each ADC has undergone extensive preclinical testing and has completed phase 1 testing in men with advanced prostate cancer. The preclinical and clinical findings have largely substantiated the promise of PSMA as an ADC target. This report summarizes the completed studies, current status, and potential future directions for ADCs that target PSMA.