Prostate stem cell
antigen (PSCA) is a highly glycosylated
cell surface protein which is overexpressed in several
malignancies including prostate, pancreas, and urinary bladder
cancers.
Tumor suppression has been reported by anti-PSCA antibody. Small and high affinity
single chain antibodies (scFv) have been introduced as effective agents for
cancer immunotargeting approaches. In the present study, we used a phage antibody display library of scFv and selected two
antibodies against two
immunodominant epitopes of PSCA by panning process. The reactivity of the scFvs for the corresponding
epitopes was determined by phage ELISA. The binding specificity of
antibodies to PSCA-expressing
prostate cancer cell line, DU-145, was analyzed by flow cytometry. The antiproliferative and apoptotic induction effects were evaluated by MTT and
Annexin-V assays, respectively. Results represented functional scFv C5-II which could bind specifically to DU-145 cells and significantly inhibited the proliferation of these cells (61%) with no effect on PSCA-negative cells. The antibody also induced apoptosis in the PSCA expressing cells. The percentage of the apoptotic cells after 24 hrs of exposure to 500 scFv/cell was 33.80%. These results demonstrate that the functional anti-PSCA scFv C5-II has the potential to be considered as a new agent for targeted
therapy of
prostate cancer.