title: Safety and immunological efficacy of a DNA vaccine encoding prostatic acid phosphatase in patients with stage D0 prostate cancer.
abstract: OBJECTIVE
  Prostatic acid phosphatase (PAP) is a prostate tumor antigen. We have previously demonstrated that a DNA vaccine encoding PAP can elicit antigen-specific CD8+ T cells in rodents. We report here the results of a phase I/IIa trial conducted with a DNA vaccine encoding human PAP in patients with stage D0 prostate cancer.
  
  
  METHODS
  Twenty-two patients were treated in a dose-escalation trial with 100 microg, 500 microg, or 1,500 microg plasmid DNA, coadministered intradermally with 200 microg granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant, six times at 14-day intervals. All patients were observed for 1 year after treatment.
  
  
  RESULTS
  No significant adverse events were observed. Three (14%) of 22 patients developed PAP-specific IFN gamma-secreting CD8+ T-cells immediately after the treatment course, as determined by enzyme-linked immunospot. Nine (41%) of 22 patients developed PAP-specific CD4+ and/or CD8+ T-cell proliferation. Antibody responses to PAP were not detected. Overall, the prostate-specific antigen (PSA) doubling time was observed to increase from a median 6.5 months pretreatment to 8.5 months on-treatment (P = .033), and 9.3 months in the 1-year post-treatment period (P = .054).
  
  
  CONCLUSIONS
  The demonstration that a DNA vaccine encoding PAP is safe, elicits an antigen-specific T-cell response, and may be associated with an increased PSA doubling time suggests that a multi-institutional phase II trial designed to evaluate clinical efficacy is warranted.
authors.affiliation: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Department of Biostatistics, University of Wisconsin, Madison, WI, USA. dm3@medicine.wisc.edu
authors.forename: Douglas G
authors.initials: DG
authors.lastname: McNeel
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Dunphy
authors.forename: James G
authors.initials: JG
authors.lastname: Davies
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Frye
authors.forename: Laura E
authors.initials: LE
authors.lastname: Johnson
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Staab
authors.forename: Dorothea L
authors.initials: DL
authors.lastname: Horvath
authors.forename: Jane
authors.initials: J
authors.lastname: Straus
authors.forename: Dona
authors.initials: D
authors.lastname: Alberti
authors.forename: Rebecca
authors.initials: R
authors.lastname: Marnocha
authors.forename: Glenn
authors.initials: G
authors.lastname: Liu
authors.forename: Jens C
authors.initials: JC
authors.lastname: Eickhoff
authors.forename: George
authors.initials: G
authors.lastname: Wilding
mesh_terms: D000135:Acid Phosphatase; D000230:Adenocarcinoma / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D011994:Recombinant Proteins; D013997:Time Factors; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D011994:Recombinant Proteins; D019444:Vaccines, DNA; C081222:sargramostim; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases; D017430:Prostate-Specific Antigen