Cancer Immunology, Immunotherapy

, Volume 56, Issue 6, pp 885–895

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

  • Laura E. Johnson
  • Thomas P. Frye
  • Nachimuthu Chinnasamy
  • Dhanalakshmi Chinnasamy
  • Douglas G. McNeel
Original Article

Abstract

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 IFNγ 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.

Keywords

Prostatic acid phosphatase DNA vaccine Prostate cancer Rat 

Abbreviations

BrdU

Bromodeoxyuridine

BSA

Bovine serum albumin

CFA

Complete Freund’s adjuvant

CTL

Cytotoxic T lymphocytes

DC

Dendritic cell

EDTA

Ethylenediaminetetraacetic acid

ELISA

Enzyme-linked immunosorbent assay

GFP

Green fluorescent protein

GM-CSF

Granulocyte macrophage colony-stimulating factor

hPAP

Human prostatic acid phosphatase

IFA

Incomplete Freund’s adjuvant

IFNγ

Interferon-gamma

IgG

Immunoglobulin G

IL-10

Interleukin-10

MHC

Major histocompatibility complex

MOI

Multiplicity of infection

OD

Optical density

PAP

Prostatic acid phosphatase

PBS

Phosphate buffered saline

pfu

Plaque-forming unit

PHA

Phytohemaglutinin

pTVG-HP

DNA vaccine encoding hPAP

pTVG-RP

DNA vaccine encoding rPAP

rPAP

Rat prostatic acid phosphatase

SE

Standard error

TMB

Tetramethylbenzidine

VV-HP

Recombinant vaccinia virus encoding hPAP

VVwt

Wild type vaccinia virus

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Laura E. Johnson
    • 1
  • Thomas P. Frye
    • 1
  • Nachimuthu Chinnasamy
    • 2
  • Dhanalakshmi Chinnasamy
    • 2
  • Douglas G. McNeel
    • 1
    • 3
  1. 1.Department of MedicineUniversity of WisconsinMadisonUSA
  2. 2.Vince Lombardi Gene Therapy Laboratory, Immunotherapy ProgramSt. Luke’s Medical CenterMilwaukeeUSA
  3. 3.K4/518 Clinical Science CenterMadisonUSA

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