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

Authors

  • Laura E. Johnson
    • Department of MedicineUniversity of Wisconsin
  • Thomas P. Frye
    • Department of MedicineUniversity of Wisconsin
  • Nachimuthu Chinnasamy
    • Vince Lombardi Gene Therapy Laboratory, Immunotherapy ProgramSt. Luke’s Medical Center
  • Dhanalakshmi Chinnasamy
    • Vince Lombardi Gene Therapy Laboratory, Immunotherapy ProgramSt. Luke’s Medical Center
    • Department of MedicineUniversity of Wisconsin
    • K4/518 Clinical Science Center
Original Article

DOI: 10.1007/s00262-006-0241-8

Cite this article as:
Johnson, L.E., Frye, T.P., Chinnasamy, N. et al. Cancer Immunol Immunother (2007) 56: 885. doi:10.1007/s00262-006-0241-8

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

Copyright information

© Springer-Verlag 2006