Generation of Recombinant Antibodies with Inhibitory Potencial Against PSA (Prostate Specific Antigen)
Human tissue kallikreins (KLKs) is a family of 15 serine protease expressed in many tissues of the human body, and are involved in several important physiological roles and pathologies, like câncer. The KLK3, also known as PSA (Prostate-specific antigen), is one of the most studied KLKs, mainly because it can be used as a biomarker for prostate câncer detection and monitoring. Antibody market have been growing in the past years on pharmaceutical sector, in 2016 half of the ten top-sellers drugs are mABs and 1 Fc-fusion protein, which represents almost $54 millions in worldwide sales and until october 2017 FDA and/or EMA approved the commercialization of 61 mABs and 11 Fc-fusion proteins. In 2016, Dr. Luciano Puzer established a collaboration with Dr. Michael Hust from Technische Universität Braunschweig, where he select 14 antibodies against KLK3. In this project we propose to express and characterize the inhibitory activity of these 14 antibodies and construct a light chain shuffling library based on the best inhibitor, aiming to generate an molecules that: 1) binds to the KLK3, for enzyme monitoring; 2) act as a proteolytic inhibitor, for therapeutic treatment. In both cases, we are interested in molecules with high affinity.