Developing Nanobodies that Bind PSMA for Clinical Translation as Therapeutic and Diagnostic agents in Prostate Cancer

Lior Rosenfeld liorrose@post.bgu.ac.il ¹ Sigal Gelkop ² Anat Shahar ³ Leslie Lobel ² Niv Papo ¹

¹Department of Biotechnology Engineering and the National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel
²Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Beer-Sheva, Israel
³The National Institute of Biotechnology in the Negev (NIBN), Ben-Gurion University of the Negev, Beer-Sheva, Israel

Prostate cancer is one of the most widespread cancer types throughout the world. The current methods for prostate cancer detection are not accurate enough, and therefore there is an increasing need for an alternative approach for its diagnosis. Prostate specific membrane antigen (PSMA) is an enzyme that is highly overexpressed in prostate cancer cells and the neovasculature of human tumors. In order to develop an accurate screening method for prostate cancer, we developed 4 single domain antibodies from camel, with affinities of 0.05-6 nM towards PSMA. These antibodies show good binding to PSMA both in SPR and in prostate cancer cells, but do not inhibit the enzymatic activity of PSMA. In addition, our nanobodies show accumulation in prostate cancer tumors expressing PSMA but not in tumors lacking it in preliminary in vivo optical imaging assays.