Generation and characterization of novel high-affinity fully human antibodies targeting prostate-specific membrane antigen and prostatic acid phosphatase

Background Prostate-specific membrane antigen (PSMA)-targeted therapies have revolutionized the management of patients with prostate cancer. However, not all patients benefit from such agents. Prostatic acid phosphatase (ACP3), a tyrosine phosphatase produced by prostate epithelial cells, has emerged as a promising alternative target for both early and advanced disease. Methods Here, we report on the generation and characterization of novel, fully human monoclonal antibodies targeting PSMA and ACP3. Antigen-specific clones were isolated from human antibody phage display libraries and characterized in vitro and in vivo. Results Selected clones bound with high specificity to the cognate target and demonstrated excellent tumor-targeting performance in biodistribution studies. Conclusions The lead candidates, termed H92A5 (anti-PSMA) and EKA4 (anti-ACP3), could serve as promising scaffolds for the development of next-generation tumor-targeted therapeutics for prostate cancer. Statement of Significance This project developed new fully human antibodies targeting prostate-specific membrane antigen and prostatic acid phosphatase, two key antigens in prostate cancer. These antibodies showed strong and specific tumor binding in animal models. They represent potential tools for improving prostate cancer treatment.