Exploration of target molecules for prostate cancer gene therapy.
BACKGROUND
Focusing on Adv-FZ33, a modified adenovirus in which a synthetic 33-amino-acid immunoglobulin G-binding domain was inserted into the adenoviral fiber protein, we tried to identify suitable target molecules for prostate cancer-specific gene therapy.


METHODS
Hybridomas were established from mice immunized with prostate cancer cell lines. The hybridomas were screened using Adv-FZ33 to create monoclonal antibodies (mAbs) that induced high gene transfer efficiency for PC-3 cells. Furthermore, we identified target antigens of the mAbs by immunoprecipitation and mass spectrometry, and investigated the expression of target molecules by flow cytometry and immunocytochemistry.


RESULTS
Using Adv-FZ33, we established four different mouse mAbs that increased transduction efficiency for PC-3. The target antigens identified were Ep-CAM, CD155, HAI-1, and Na,K-ATPase beta1. These antigens were expressed in several cancer cell lines, including prostate cancer. Human prostatic myofibroblast cells lacked expression of Ep-CAM and HAI-1.


CONCLUSIONS
We established anti-Ep-CAM mAb and anti- HAI-1 mAbs. Gene transduction via Ep-CAM and HAI-1 may be a novel strategy for treatment of prostate cancer.
Suzuki
Kazuhiro
K
Department of Molecular Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Nakamura
Kiminori
K
Kato
Kazunori
K
Hamada
Hirofumi
H
Tsukamoto
Taiji
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology; D001666:Binding Sites, Antibody; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000276:immunology; D045744:Cell Line, Tumor; D000071858:Epithelial Cell Adhesion Molecule; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000276:immunology / Q000628:therapy*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000032:analysis / Q000276:immunology; D013205:Staphylococcal Protein A / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D007074:Immunoglobulin G; D053491:Proteinase Inhibitory Proteins, Secretory; C109149:SPINT1 protein, human; D013205:Staphylococcal Protein A; D014764:Viral Proteins