Combination of Recombinant Xenogeneic Endoglin DNA and Protein Vaccination Enhances Anti-tumor Effects

Abstract

The immunization approaches with DNA vaccine priming and subsequent protein or peptide boosting has been widely tested in various models of infectious diseases. However, these approaches are seldom reported in the areas of cancer immunotherapy. In this study we combined endoglin plasmid DNA and recombinant protein as vaccines and used them to prime and boost, simultaneously, as a vaccine strategy. Our results showed that combination of endoglin DNA and protein vaccines could enhance both protective and therapeutic anti-tumor efficacy in both colon carcinoma and Lewis lung carcinoma models. Significant inhibition of tumor angiogenesis was found in the tumor tissues. The titers of autoantibodies against murine endoglin were significantly increased and the antibody levels lasted longer in the mice with combined endoglin DNA and recombinant protein vaccination. CTL response against endoglin-positive HUVECs, but not against endoglin-negative tumor cells was found in the mice combined DNA with protein vaccination. In addition, combination of endoglin DNA and recombinant protein vaccination significantly induced IFN-γ secreting cells. These observations suggested that a combination of endoglin DNA and recombinant protein immunization as a vaccine strategy was superior to those using endoglin DNA or recombinant protein alone as vaccines.

Keywords:

• Endoglin
• cancer
• immunogene therapy
• angiogenesis
• autoantibody
• T lymphocyte
• interferon-γ

ABBREVIATIONS
ELISA:	=	Enzyme-linked immunoadsorbent assay
ELISPOT:	=	Enzyme-linked immunospot; HUVECs
HUVECs:	=	Human umbilical vein endothelial cells
mEDG:	=	Recombinant murine endoglin
NS:	=	Normal saline
pEDG:	=	Recombinant porcine endoglin
pmEDG:	=	Recombinant plasmid DNA encoding extracellular domain of murine endoglin
ppEDG:	=	Recombinant plasmid DNA encoding extracellular domain of porcine endoglin