Evidence of determinant spreading in the antibody responses to prostate cell surface antigens in patients immunized with prostate-specific antigen.
OBJECTIVE
Prostate cancer consistently remains a difficult clinical problem. The development of novel therapy strategies for effective control and treatment of prostate cancer is essential. The prostate represents a unique site for immunotherapy, in part because prostate-specific immunity would most probably be without significant long-term sequellae. Antibodies and cell-mediated immunity, induced by either active or passive immunization, represent potential means to specifically target prostate tumor cells.


METHODS
The serum IgG response to cell surface antigens expressed on LNCAP [prostate-specific antigen (PSA)-positive] and PC-3 (PSA-negative) were analyzed in individuals with advanced disease receiving vaccinia- or fowlpox-expressed PSA (v-PSA or f-PSA, respectively) by flow cytometry.


RESULTS
Sera from all seven patients in a Phase I study of v-PSA, collected prior to the third immunization, reacted with both prostate tumor cell lines. The majority of individuals (n = 12) in a Phase II trial of v-PSA and f-PSA developed sustainable antibody responses to cell surface antigens on the prostate tumor cell lines. The magnitude and kinetics of these responses were dependent on the immunization schedule. Of importance, the baseline serum of only one of nine patients tested had reactivity with nonprostate tumor cell lines. Sera from three normal males also lacked reactivity with prostate tumor cells.


CONCLUSIONS
PSA vaccine constructs are immunogenic and induce antibody responses to a multitude of surface antigens on prostate tumor cell lines by epitope or determinant spreading after stimulation of the immune system by PSA immunization.
Cavacini
Lisa A
LA
Beth Israel Deaconess Medical Center, 21-27 Burlington Avenue, Room 556, Boston, MA 02215, USA. lcavacin@caregroup.harvard.edu
Duval
Mark
M
Eder
J Paul
JP
Posner
Marshall R
MR
D019496:Cancer Vaccines; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry*; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D017430:Prostate-Specific Antigen / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000517:prevention & control*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D000939:Epitopes; D007074:Immunoglobulin G; D017430:Prostate-Specific Antigen