DNA vaccines: an active immunization strategy for prostate cancer.
Immunotherapy is currently being investigated as a treatment for patients with asymptomatic, recurrent prostate cancer manifested only by a rising prostate-specific antigen (PSA) level. Several different approaches to active immunization against antigens found on cancer cells have been explored. Immunization with DNA overcomes many of the obstacles noted in previous studies. Injection of plasmid DNA encoding a xenogeneic differentiation antigen (prostate-specific membrane antigen [PSMA]) is a potent means to induce antibody and T-cell responses to these otherwise poorly immunogenic self proteins. Use of the xenogeneic DNA (ie, human PSMA DNA injected into mouse) has been shown to be an absolute requirement to overcome immunologic tolerance. We are currently conducting a phase I trial of human and mouse PSMA DNA vaccines in patients with recurrent prostate cancer, based on preclinical experiments described below.
Wolchok
Jedd D
JD
Clinical Immunology Services, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Gregor
Polly D
PD
Nordquist
Luke T
LT
Slovin
Susan F
SF
Scher
Howard I
HI
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology / Q000627:therapeutic use; D000954:Antigens, Surface / Q000276:immunology / Q000627:therapeutic use; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology / Q000627:therapeutic use; D001324:Autoantigens / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood; D017321:Clinical Trials, Phase I as Topic; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D043425:Glutamate Carboxypeptidase II / Q000276:immunology / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008297:Male; D051379:Mice; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000276:immunology / Q000628:therapy*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000145:classification / Q000276:immunology / Q000627:therapeutic use*; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use
D015478:Antigens, Heterophile; D000954:Antigens, Surface; D015295:Antigens, Tumor-Associated, Carbohydrate; D001324:Autoantigens; D014408:Biomarkers, Tumor; D006360:Heat-Shock Proteins; D019444:Vaccines, DNA; D014765:Viral Vaccines; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen