Plasmid DNA vaccine encoding prostatic acid phosphatase is effective in eliciting autologous antigen-specific CD8+ T cells

Cancer Immunol Immunother. 2007 Jun;56(6):885-95. doi: 10.1007/s00262-006-0241-8. Epub 2006 Nov 11.


Prostatic acid phosphatase (PAP) is a prostate cancer tumor antigen and a prostate-specific protein shared by rats and humans. Previous studies indicated that Copenhagen rats immunized with a recombinant vaccinia virus expressing human PAP (hPAP) developed PAP-specific cytotoxic T cells (CTL) with cross reactivity to rat PAP (rPAP) and evidence of prostate inflammation. Viral delivery of vaccine antigens is an active area of clinical investigation. However, a potential difficulty with viral-based immunizations is that immune responses elicited to the viral vector might limit the possibility of multiple immunizations. In this paper, we investigate the ability of another genetic immunization method, a DNA vaccine encoding PAP, to elicit antigen-specific CD8+ T cell immune responses. Specifically, Lewis rats were immunized with either a plasmid DNA-based (pTVG-HP) or vaccinia-based (VV-HP) vaccine each encoding hPAP. We determined that rats immunized with a DNA vaccine encoding hPAP developed a Th1-biased immune response as indicated by proliferating PAP-specific CD4+ and CD8+ cells and IFNgamma production. Rats immunized with vaccinia virus encoding PAP did not develop a PAP-specific response unless boosted with a heterologous vaccination scheme. Most importantly, multiple immunizations with a DNA vaccine encoding the rat PAP homologue (pTVG-RP) could overcome peripheral self-tolerance against rPAP and generate a Th1-biased antigen-specific CD4+ and CD8+ T cell response. Overall, DNA vaccines provide a safe and effective method of generating prostate antigen-specific T cell responses. These findings support the investigation of PAP-specific DNA vaccines in human clinical trials.

Publication types

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

MeSH terms

  • Acid Phosphatase
  • Animals
  • Autoantigens / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Genetic Vectors / immunology
  • Humans
  • Male
  • Plasmids
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / therapy*
  • Protein Tyrosine Phosphatases / immunology*
  • Rats
  • Rats, Inbred Lew
  • Transduction, Genetic
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*
  • Vaccinia virus / genetics


  • Autoantigens
  • Cancer Vaccines
  • Vaccines, DNA
  • Acid Phosphatase
  • prostatic acid phosphatase
  • Protein Tyrosine Phosphatases