Annals of Surgical Oncology

, Volume 12, Issue 7, pp 517–525 | Cite as

A Tat Fusion Protein–Based Tumor Vaccine for Breast Cancer

  • Carsten T. Viehl
  • Michelle Becker-Hapak
  • Jason S. Lewis
  • Yoshiyuki Tanaka
  • Udaya K. Liyanage
  • David C. Linehan
  • Timothy J. Eberlein
  • Peter S. Goedegebuure
Article

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 protein Her2/neu Cancer vaccine Breast cancer Animal study 

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Copyright information

© The Society of Surgical Oncology, Inc. 2005

Authors and Affiliations

  • Carsten T. Viehl
    • 1
    • 2
  • Michelle Becker-Hapak
    • 3
  • Jason S. Lewis
    • 4
    • 5
  • Yoshiyuki Tanaka
    • 1
  • Udaya K. Liyanage
    • 1
  • David C. Linehan
    • 1
    • 5
  • Timothy J. Eberlein
    • 1
    • 5
  • Peter S. Goedegebuure
    • 1
    • 5
  1. 1.Department of SurgeryWashington University School of MedicineSt. Louis
  2. 2.Department of Surgery, Divisions of General Surgery and Surgical ResearchUniversity of BaselSwitzerland
  3. 3.Division of OncologyAlvin J. Siteman Cancer Center, Washington University School of MedicineSt. Louis
  4. 4.Mallinckrodt Institute of RadiologyWashington University School of MedicineSt. Louis
  5. 5.Alvin J. Siteman Cancer CenterWashington University School of MedicineSt. Louis

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