The prostate specific membrane antigen (PSMA) is abundantly expressed in prostate cancer, which is a type-II transmembrane protein expressed in almost all patients with prostate cancer. The expression of PSMA is high in patients with poorly differentiated, metastatic, and hormone-refractory prostate cancer, while only has limited expression in other organs. This expression pattern guarantees PSMA being an ideal target for the diagnosis and therapy of prostate cancer. Besides, PSMA has also been found to be highly expressed in solid tumor vasculature, but not in normal vascular endothelium, indicating that the PSMA targeted tools may have even wider application. Like other tumor antigens, PSMA has also been exploited in the discovery of specific antibodies. But currently all of the PSMA targeting antibodies under development are full antibodies, and most of them are murine monoclonal antibodies. The murine origin, slow clearance rate and poor tumor penetration of these full antibodies severely limited their application in tumor imaging and therapy. Smaller antibodies have more advantages for targeted imaging and therapy because they have faster clearance rate and deeper tissue penetration capability. Therefore, the discovery of novel smaller PSMA specific human antibodies are needed for the development of specific agents for prostate cancer imaging and therapy.
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