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.