Safety and immunological efficacy of a DNA vaccine encoding prostatic acid phosphatase in patients with stage D0 prostate cancer

J Clin Oncol. 2009 Sep 1;27(25):4047-54. doi: 10.1200/JCO.2008.19.9968. Epub 2009 Jul 27.


Purpose: 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.

Patients and 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).

Conclusion: 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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acid Phosphatase
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Adjuvants, Immunologic / administration & dosage
  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Humans
  • Immunotherapy / methods*
  • Injections, Intradermal
  • Interferon-gamma / metabolism
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Protein Tyrosine Phosphatases / immunology*
  • Recombinant Proteins
  • Time Factors
  • Treatment Outcome
  • Vaccines, DNA / administration & dosage


  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Recombinant Proteins
  • Vaccines, DNA
  • sargramostim
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Acid Phosphatase
  • prostatic acid phosphatase
  • Protein Tyrosine Phosphatases
  • Prostate-Specific Antigen