Cancer Immunology, Immunotherapy

, Volume 58, Issue 8, pp 1337–1349

Memory and cellular immunity induced by a DNA vaccine encoding self antigen TPD52 administered with soluble GM-CSF

  • Jennifer D. Lewis
  • Laura A. Sullivan
  • Jennifer A. Byrne
  • Werner de Riese
  • Robert K. Bright
Original Article

DOI: 10.1007/s00262-009-0659-x

Cite this article as:
Lewis, J.D., Sullivan, L.A., Byrne, J.A. et al. Cancer Immunol Immunother (2009) 58: 1337. doi:10.1007/s00262-009-0659-x

Abstract

Tumor protein D52 (TPD52) is involved in cellular transformation, proliferation and metastasis. TPD52 over expression has been demonstrated in several cancers including prostate, breast, and ovarian carcinomas. Murine TPD52 (mD52) has been shown to induce anchorage independent growth in vitro and metastasis in vivo, and mirrors the function and normal tissue expression patterns of the human orthologue of TPD52. We believe TPD52 represents a self, non-mutated tumor associated antigen (TAA) important for maintaining a transformed and metastatic cellular phenotype. The transgenic adeno-carcinoma of the mouse prostate (TRAMP) model was employed to study mD52 as a vaccine antigen. Naïve mice were immunized with either recombinant mD52 protein or plasmid DNA encoding the full-length cDNA of mD52. Following immunization, mice were challenged with a subcutaneous, tumorigenic dose of mD52 positive, autochthonous TRAMP-C1 tumor cells. Sixty percent of mice were tumor free 85 days post challenge with TRAMP-C1 when immunized with mD52 as a DNA-based vaccine admixed with soluble granulocyte-macrophage colony stimulating factor (GM-CSF). Survivors of the initial tumor challenge rejected a second tumor challenge given in the opposite flank approximately 150 days after the first challenge, and remained tumor free for more than an additional 100 days. The T cell cytokine secretion patterns from tumor challenge survivors indicated that a TH1-type cellular immune response was involved in tumor protection. These data suggest that mD52 vaccination induced a memory, cellular immune response that resulted in protection from murine prostate tumors that naturally over express mD52 protein.

Keywords

DNA vaccine mD52 TPD52 TRAMP-C1 GM-CSF 

Abbreviations

TPD52

Tumor protein D52

mD52

Murine TPD52

hD52

Human TPD52

TRAMP

Transgenic adenocarcinoma of the mouse prostate

TAA

Tumor associated antigen

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Jennifer D. Lewis
    • 1
  • Laura A. Sullivan
    • 2
  • Jennifer A. Byrne
    • 3
  • Werner de Riese
    • 4
  • Robert K. Bright
    • 1
    • 4
  1. 1.Department of Microbiology and ImmunologyTexas Tech University Health Sciences CenterLubbockUSA
  2. 2.Department of SurgeryUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.Discipline of Paediatrics and Child Health, Children’s Hospital at WestmeadThe University of SydneySydneyAustralia
  4. 4.Department of UrologyTexas Tech University Health Sciences CenterLubbockUSA

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