, Volume 12, Issue 7, pp 517-525
Date: 10 May 2005

A Tat Fusion Protein–Based Tumor Vaccine for Breast Cancer

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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.

Presented at the 57th Annual Cancer Symposium of the Society of Surgical Oncology, New York, New York, March 18–21, 2004.
Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.