Combined therapy with flk1-based DNA vaccine and interleukin-12 results in enhanced antiangiogenic and antitumor effects.

ABSTRACT

In this study, we investigated the anti-vasculature effects and the antitumor effects of combining attenuated Salmonella typhimurium vaccine strain encoding murine vascular endothelial growth factor (VEGF) receptor-2 (flk1) with plasmid DNA vector encoding the murine interleukin-12 (mIL-12) gene. In combination, flk1 based DNA vaccine and mIL-12 slowed down tumor growth more effectively than either one alone. Splenocytes from the combined group were showed a strong CTL response against both the flk1 and tumor cells. Automated image analysis revealed that the mean microvessel density was significantly reduced after administering either flk1 based DNA vaccine or mIL-12. In addition, the combination of flk1 based DNA vaccine and mIL-12 appeared more effective at reducing the microvessel density of tumor (P<0.01, both comparisons). In summary, the antivasculature effect and the anti-tumor effect were better when the combination of flk1 based DNA vaccine and IL-12 was administered in comparison to the individual treatment groups, suggesting the synergistic action of flk1 based DNA vaccine and mIL-12.