Saporin toxin-conjugated monoclonal antibody targeting prostate-specific membrane antigen has potent anticancer activity

Prostate. 2010 Sep 1;70(12):1286-94. doi: 10.1002/pros.21164.


Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Biotinylation
  • Cell Line, Tumor
  • Cell Membrane / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Orchiectomy
  • Prostate-Specific Antigen / immunology*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / epidemiology
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / surgery
  • Ribosome Inactivating Proteins, Type 1 / immunology*
  • Saporins
  • Transplantation, Heterologous
  • United States / epidemiology


  • Antibodies, Monoclonal
  • Antineoplastic Agents, Phytogenic
  • Ribosome Inactivating Proteins, Type 1
  • Saporins
  • Prostate-Specific Antigen