Preparation and characterization of new anti-PSMA monoclonal antibodies with potential clinical use.
Monoclonal antibodies with high specificity for prostate cancer tissue are of interest for diagnostic and therapeutic applications employing targeted therapy. The prostate-specific membrane antigen (PSMA) is a protein predominantly found in epithelial cells of prostate tissue origin and its expression correlates with tumor aggressiveness. Here, we report the development and characterization of new antibodies against PSMA. Murine monoclonal antibodies (MAb) were obtained by immunizing mice with a peptide corresponding to PSMA extracellular residues 490-500 -- GKSLYESWTKK (PSMA(490-500)). The MAbs react specifically to PSMA and to the prostate cancer cell line LNCaP with an affinity for PSMA in the low nanomolar range. This study also demonstrates the potential use of these antibodies for targeted drug delivery to prostate cancer cells. Nanomolar concentrations of PSMA-specific MAb in association with a molecule with cytotoxic potential were sufficient to allow for binding and uptake by LNCaP cells within minutes, leading to complete cell death within 3 days. These MAbs have potential clinical value in the development of diagnostic and therapeutic applications for prostate cancer.
Moffett
Serge
S
ProScan Rx Pharma Inc, Montréal, Québec, Canada. smoffett@proscanrxpharma.com
Mélançon
Dominic
D
DeCrescenzo
Gregory
G
St-Pierre
Caroline
C
Deschénes
François
F
Saragovi
H Uri
HU
Gold
Phil
P
Cuello
A Claudio
AC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000737:chemistry* / Q000627:therapeutic use; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D001666:Binding Sites, Antibody; D014408:Biomarkers, Tumor / Q000276:immunology; D045744:Cell Line, Tumor; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D020014:K562 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D000939:Epitopes; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II