Biochemical nature and mapping of PSMA epitopes recognized by human antibodies induced after immunization with gene-based vaccines.
BACKGROUND
A possible new target for immunotherapy is the prostate-specific membrane antigen (PSMA). The aim of the present study was to define potential PSMA epitopes for antibody binding using sera from patients immunized with gene-based anti-PSMA vaccines.


METHODS
Sera from prostate cancer patients, immunized repeatedly with plasmid and adenoviral vectors, each encoding for the extracellular portion of human PSMA, were tested for anti-PSMA antibodies by Western blot. PSMA-producing LNCaP cells were used as a control. Recombinant PSMA protein cleaved with different proteinases was used for epitope mapping. Different enzymes were used to cleave the PSMA molecule.


RESULTS
Specific anti-PSMA antibodies were detected in the studied patients' sera, mainly against the PSMA protein core. An alignment of the predicted enzyme-cleavage fragments was compared with Western blot results and several antibody epitopes were determined.


CONCLUSIONS
These data demonstrate that multiple gene-based vaccinations induce an anti-PSMA humoral immune response. The antibodies are predominantly specific for the PSMA protein core.
Todorova
K
K
Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Zoubak
S
S
Mincheff
M
M
Kyurkchiev
S
S
D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D018604:Epitope Mapping; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use
D000912:Antibodies, Neoplasm; D000954:Antigens, Surface; D019496:Cancer Vaccines; D019444:Vaccines, DNA; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II