Article

Annals of Surgical Oncology

, Volume 12, Issue 7, pp 517-525

First online:

A Tat Fusion Protein–Based Tumor Vaccine for Breast Cancer

  • Carsten T. ViehlAffiliated withDepartment of Surgery, Washington University School of MedicineDepartment of Surgery, Divisions of General Surgery and Surgical Research, University of Basel
  • , Michelle Becker-HapakAffiliated withDivision of Oncology, Alvin J. Siteman Cancer Center, Washington University School of Medicine
  • , Jason S. LewisAffiliated withMallinckrodt Institute of Radiology, Washington University School of MedicineAlvin J. Siteman Cancer Center, Washington University School of Medicine
  • , Yoshiyuki TanakaAffiliated withDepartment of Surgery, Washington University School of Medicine
  • , Udaya K. LiyanageAffiliated withDepartment of Surgery, Washington University School of Medicine
  • , David C. LinehanAffiliated withDepartment of Surgery, Washington University School of MedicineAlvin J. Siteman Cancer Center, Washington University School of Medicine
  • , Timothy J. EberleinAffiliated withDepartment of Surgery, Washington University School of MedicineAlvin J. Siteman Cancer Center, Washington University School of Medicine
  • , Peter S. GoedegebuureAffiliated withDepartment of Surgery, Washington University School of MedicineAlvin J. Siteman Cancer Center, Washington University School of Medicine

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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