Humoral immune response in prostate cancer patients after immunization with gene-based vaccines that encode for a protein that is proteasomally degraded.
Prostate-specific membrane antigen (PSMA), whose expression is upregulated in poorly differentiated, metastatic, and hormone refractory prostate cancer, could be targeted by gene-based vaccines. The aim of this study was to characterize the humoral immune response against PSMA in prostate carcinoma patients who have been vaccinated against PSMA with gene-based vaccines. Sera from prostate cancer patients who had been immunized repeatedly with plasmid DNA and a recombinant adenoviral vector, both carrying an expression cassette for human PSMA, and sera from healthy donors were tested for anti-PSMA antibodies by Western blot analysis and immunofluorescence. PSMA-producing LNCaP cells, recombinant PSMA protein, and a specific antibody against PSMA were used as positive controls. Specific anti-PSMA antibodies were detected by both Western blot and immunofluorescence in the sera of patients who had been vaccinated against PSMA with plasmid and recombinant adenoviral vectors. The specificity of the anti-PSMA antibodies was confirmed by preincubation and blocking experiments. Positive reactions were detected in 86% of the vaccinated prostate cancer patients. Anti-PSMA antibodies were not detected either in the patients' sera prior to vaccination or in the sera from healthy men and women. These data demonstrate that PSMA, a specific marker for prostate cancer, is a target for humoral immune response induced by gene-based PSMA vaccination. Detection of anti-PSMA antibodies by immunoblot analysis and by indirect immunofluorescence could be used to monitor the vaccination effect.
Todorova
Krasimira
K
Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Ignatova
Irena
I
Tchakarov
Stoyan
S
Altankova
Iskra
I
Zoubak
Serguei
S
Kyurkchiev
Stanimir
S
Mincheff
Milcho
M
D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects*; D000954:Antigens, Surface / Q000008:administration & dosage* / Q000235:genetics; D043425:Glutamate Carboxypeptidase II / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D007114:Immunization; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000276:immunology; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage*
D000906:Antibodies; D000954:Antigens, Surface; D019444:Vaccines, DNA; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen