A tat fusion protein-based tumor vaccine for breast cancer. Academic Article uri icon

Overview

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 gamma 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.

publication date

  • May 10, 2005

Research

keywords

  • Breast Neoplasms
  • Cancer Vaccines
  • Gene Products, tat
  • Receptor, ErbB-2
  • Recombinant Fusion Proteins

Identity

Scopus Document Identifier

  • 21244434878

Digital Object Identifier (DOI)

  • 10.1245/ASO.2005.06.028

PubMed ID

  • 15889213

Additional Document Info

volume

  • 12

issue

  • 7