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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Antibodies, Monoclonal, Antineoplastic Agents, Phytogenic, Biotinylation, Cell Line, Tumor, Cell Membrane, Enzyme-Linked Immunosorbent Assay, Humans, Male, Mice, Mice, Nude, Orchiectomy, Prostate-Specific Antigen, Prostatic Neoplasms, Ribosome Inactivating Proteins, Type 1, Saporins, Transplantation, Heterologous, United States.
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Does saporin toxin-conjugated monoclonal antibody targeting prostate-specific membrane antigen have potent anticancer activity? Context: Prostate-specific membrane antigen (PSMA) provides an attractive target for monoclonal antibody targeted therapies in the treatment of prostate cancer (PC). In this study, we generated an immunotoxin by linking a humanized anti-PSMA monoclonal antibody (hJ591) to the ribosome-inactivating protein toxin saporin. The hJ591-saporin immunoconjugate was evaluated for antitumor activity against PC cells. PSMA-positive cell lines, LNCaP and CWR22Rv1 and a PSMA-negative cell line, PC-3, were used in these experiments. The hJ591 was biotinylated and mixed with streptavidin-saporin (SAZAP). The binding ability of hJ591-SAZAP and the extent of internalization into the cells were tested. The viability of cells treated with hJ591-SAZAP was also examined and the apoptotic cells were measured. Lastly, the anticancer effect of hJ591-SAZAP was investigated in vivo. The binding ability of hJ591-SAZAP to PSMA was equivalent to that of unconjugated J591. Internalization of hJ591-SAZAP was clearly detected in PSMA-positive, but not in PSMA-negative cell lines. IC(50) of hJ591-SAZAP was 0.14 nM, 1.99 nM, and more than 100 nM in LNCaP, CWR22Rv1, and PC-3 cells, respectively. After 72 hr of hJ591-SAZAP treatment, the percentage of apoptotic cells was 60.29% and 40.73% in LNCaP and CWR22Rv1 cells, respectively, compared to 4.70% in PC-3 cells. The hJ591-SAZAP also had anticancer activity in a LNCaP xenograft model.
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Our findings show that hJ591-SAZAP conjugate has potent and selective antitumor effects on PSMA-positive PC cells in vitro and in vivo. This study supports development of PSMA antibody-toxin conjugates for therapy of PC. Final Decision: yes