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A Tat Fusion Protein–Based Tumor Vaccine for Breast Cancer

¹ Department of Surgery, Washington University School of Medicine, 660 S. Euclid Avenue, Box 8109, St. Louis, Missouri 63110
² Department of Surgery, Divisions of General Surgery and Surgical Research, University of Basel, Spitalstrasse 21, 4031 Basel, Switzerland
³ Division of Oncology, Alvin J. Siteman Cancer Center, Washington University School of Medicine, Box 8007, 660 S. Euclid Avenue, St. Louis, Missouri 63110
⁴ Mallinckrodt Institute of Radiology, Washington University School of Medicine, Box 8225, 510 South kingshighway Boulevard, St. Louis, Missouri 63110
⁵ Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110

Correspondence: Address correspondence and reprint requests to: Peter S. Goedegebuure, PhD, Department of Surgery, Washington University School of Medicine, 660 S. Euclid Avenue, Box 8109, St. Louis, MO 63110, USA; E-mail: goedegep{at}wustl.edu.

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 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.

Key Words: Tat fusion protein • Her2/neu • Cancer vaccine • Breast cancer • Animal study

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