Co-delivery of PSA and PSMA DNA vaccines with electroporation induces potent immune responses

Hum Vaccin. 2011 Jan-Feb:7 Suppl:120-7. doi: 10.4161/hv.7.0.14574. Epub 2011 Jan 1.

Abstract

Prostate cancer (PCa) remains a significant public health problem. Current treatment modalities for PCa can be useful, but may be accompanied by deleterious side effects and often do not confer long-term control. Accordingly, additional modalities, such as immunotherapy, may represent an important approach for PCa treatment. The identification of tissue-specific antigens engenders PCa an attractive target for immunotherapeutic approaches. Delivery of DNA vaccines with electroporation has shown promising results for prophylactic and therapeutic targets in a variety of species including humans. Application of this technology for PCa immunotherapy strategies has been limited to single antigen and epitope targets. We sought to test the hypothesis that a broader collection of antigens would improve the breadth and effectiveness of a PCa immune therapy approach. We therefore developed highly optimized DNA vaccines encoding prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) as a dual antigen approach to immune therapy of PCa. PSA-and PSMA-specific cellular immunogenicity was evaluated in a mouse model for co-delivery and single antigen vaccination. Mice received 2 immunizations spaced 2 weeks apart and immunogenicity was evaluated 1 week after the second vaccination. Both the PSA and PSMA vaccines induced robust antigen-specific IFNγ responses by ELISpot. Further characterization of cellular immunogenicity by flow cytometry indicated strong antigen-specific TNFα production by CD4+ T cells and IFNγ and IL-2 secretion by both CD4+ and CD8+ T cells. There was also a strong humoral response as determined by PSA-specific seroconversion. These data support further study of this novel approach to immune therapy of PCa.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Disease Models, Animal
  • Electroporation / methods*
  • Enzyme-Linked Immunospot Assay
  • Female
  • Immunization, Secondary / methods
  • Immunotherapy / methods*
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Prostate-Specific Antigen / genetics*
  • Prostate-Specific Antigen / immunology*
  • Prostatic Neoplasms / therapy*
  • Rodent Diseases / therapy
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccination / methods
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*

Substances

  • Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Vaccines, DNA
  • Interferon-gamma
  • Prostate-Specific Antigen