PSMA ADC (Progenics Pharmaceuticals)

PSMA ADC is an investigational antibody-drug conjugate (ADC) developed by Progenics Pharmaceuticals (now Lantheus) for the treatment of cancers expressing prostate-specific membrane antigen (PSMA). The drug consists of a fully human IgG1 monoclonal antibody (clone 4D4) directed against the extracellular domain of PSMA, conjugated via a protease-cleavable valine-citrulline (vc) linker to the potent microtubule-disrupting agent monomethyl auristatin E (MMAE). While PSMA is a well-known marker in prostate cancer, it is also highly expressed on the neovasculature of various non-prostatic solid tumors, including high-grade gliomas. In glioblastoma multiforme and gliosarcoma, PSMA ADC targets the tumor's vascular endothelial cells; upon binding and internalization, the MMAE payload is released, leading to cell cycle arrest and apoptosis of the endothelial cells, thereby disrupting the tumor's blood supply. This vascular-targeting strategy is intended to overcome the limitations of direct tumor cell targeting in heterogeneous brain tumors.

Other names

Prostate-Specific Membrane Antigen Antibody-Drug ConjugatePSMA-MMAE ADC