Induction of PSA-specific CTLs and anti-tumor immunity by a genetic prostate cancer vaccine

Prostate. 2005 Feb 15;62(3):217-23. doi: 10.1002/pros.20135.

Abstract

Background: Prostate cancer is the most common malignancy in Swedish and American men. Effective curative treatment modalities are debilitating and available only for localized disease. As an immunotherapy approach, DNA encoding prostate-specific antigen (PSA), was used to immunize mice and induce PSA-specific cellular immunity.

Methods: A plasmid expressing PSA, alone or in combination with plasmids coding for GM-CSF and/or IL-2, was used for DNA immunization. Cr-release, intracellular IFN-gamma cytokine staining, and tumor challenge assays were used to evaluate the immune response.

Results: The DNA vaccine induces PSA-specific cytotoxic T lymphocytes (CTLs) and when co-injected with IL-2 and GM-CSF it protects four of five mice against a PSA-expressing tumor challenge.

Conclusions: We demonstrate that immunization with a PSA DNA vaccine can evoke PSA-specific cellular immune responses. We also show, for the first time, that a PSA DNA vaccine can induce anti-tumor immunity in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Line, Tumor
  • Female
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Immunity, Cellular / immunology
  • Immunization
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-2 / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Prostate-Specific Antigen / genetics
  • Prostate-Specific Antigen / immunology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / prevention & control*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccines, DNA / immunology
  • Vaccines, DNA / therapeutic use*

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Interleukin-2
  • Vaccines, DNA
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Prostate-Specific Antigen