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Saporin toxin‐conjugated monoclonal antibody targeting prostate‐specific membrane antigen has potent anticancer activity
Author(s) -
Kuroda Kenji,
Liu He,
Kim Sae,
Guo Ming,
Navarro Vincent,
Bander Neil H.
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21164
Subject(s) - lncap , immunotoxin , saporin , monoclonal antibody , cancer research , in vivo , cell culture , antigen , internalization , antibody , microbiology and biotechnology , prostate cancer , chemistry , cell , medicine , biology , immunology , cancer , biochemistry , genetics
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. Prostate 70:1286–1294, 2010. © 2010 Wiley‐Liss, Inc.