Annals of Surgical Oncology

, Volume 12, Issue 7, pp 517–525

A Tat Fusion Protein–Based Tumor Vaccine for Breast Cancer

Authors

  • Carsten T. Viehl
    • Department of SurgeryWashington University School of Medicine
    • Department of Surgery, Divisions of General Surgery and Surgical ResearchUniversity of Basel
  • Michelle Becker-Hapak
    • Division of OncologyAlvin J. Siteman Cancer Center, Washington University School of Medicine
  • Jason S. Lewis
    • Mallinckrodt Institute of RadiologyWashington University School of Medicine
    • Alvin J. Siteman Cancer CenterWashington University School of Medicine
  • Yoshiyuki Tanaka
    • Department of SurgeryWashington University School of Medicine
  • Udaya K. Liyanage
    • Department of SurgeryWashington University School of Medicine
  • David C. Linehan
    • Department of SurgeryWashington University School of Medicine
    • Alvin J. Siteman Cancer CenterWashington University School of Medicine
  • Timothy J. Eberlein
    • Department of SurgeryWashington University School of Medicine
    • Alvin J. Siteman Cancer CenterWashington University School of Medicine
  • Peter S. Goedegebuure
    • Department of SurgeryWashington University School of Medicine
    • Alvin J. Siteman Cancer CenterWashington University School of Medicine
Article

DOI: 10.1245/ASO.2005.06.028

Cite this article as:
Viehl, C.T., Becker-Hapak, M., Lewis, J.S. et al. Ann Surg Oncol (2005) 12: 517. doi:10.1245/ASO.2005.06.028

Abstract

Background

We recently reported that dendritic cells (DCs) transduced with a fusion protein between Her2/neu and the protein transduction domain Tat (DC-Tat-extracellular domain [ECD]) induced Her2/neu-specific CD8+ T cells in vitro. This study tested the in vivo efficacy of DC-Tat-ECD in a murine breast cancer model.

Methods

FVB/N mice received one or two weekly intraperitoneal immunizations with syngeneic DC-Tat-ECD followed by a tumor challenge with syngeneic neu+ breast cancer cells, and tumor development was monitored. To test for Her2/neu specificity, CD4+ and CD8+ cells were isolated through magnetic bead separation and analyzed for specific interferon γ release.

Results

Intraperitoneally injected DCs migrated to secondary lymphoid organs, as evidenced by small-animal positron emission tomography studies. Immunized mice developed palpable tumors significantly later than control mice injected with DC-Tat-empty (P = .001 and P < .05 for two immunizations and for one immunization, respectively) or mice that received no DCs (P = .001 and P < .05). Similarly, immunized mice had smaller resulting tumors than mice injected with DC-Tat-empty (P < .05 and P < .01) or untreated mice (P < .001 and P < .001). Significantly more tumor-specific CD8+ splenocytes were found in twice-immunized mice than in untreated animals (P < .001). Similarly, a T-helper type 1 CD4+ T-cell response was observed.

Conclusions

Protein-transduced DCs may be effective vaccines for the treatment of cancer.

Keywords

Tat fusion proteinHer2/neuCancer vaccineBreast cancerAnimal study

Copyright information

© The Society of Surgical Oncology, Inc. 2005