Effect of a novel DNA vaccine on angiogenesis and tumor growth in vivo.

OBJECTIVE To develop a DNA cancer vaccine that targets the vascular endothelial growth factor receptor. DESIGN Mice were vaccinated intramuscularly with listeriolysin O-fetal liver kinase 1 (LLO-Flk1) or controls. Mice were also challenged subcutaneously with the tumor cell line TC-1. Tumor sizes were measured after vaccination. At the conclusion of the experiments, the tumors were harvested for immunohistochemical analysis and determination of hemoglobin content. SETTING Research laboratory. SUBJECTS Six- to 8-week-old C57BL/6 mice. INTERVENTION Fifty micrograms of each vector was administered 3 times at weekly intervals. MAIN OUTCOME MEASURES Tumor size, mean vessel density of tumors, hemoglobin content of tumor. RESULTS Mice treated with the LLO-Flk1 vaccine experienced slower tumor growth relative to the other treatment groups. Complete tumor regression was observed in several cases. Immunohistochemical staining of tumors revealed fewer blood vessels in the mice vaccinated with the LLO-Flk1 vaccine relative to the other treatment groups. Finally, colorimetric assessment for hemoglobin suggested decreased vasculature in the tumor bed of these mice relative to the control groups. CONCLUSION The novel DNA cancer vaccine LLO-Flk1 can slow tumor growth in vivo.