Combination therapy of hepatocellular carcinoma by DNA shuffling-based VEGF vaccine and doxorubicin.

Antiangiogenic therapy can enhance the efficacy of chemotherapy against solid tumors. This study was to determine whether TT46, a potential VEGF vaccine from DNA shuffling with a helper T-cell epitope of tetanus toxin B subunit, could enhance the efficacy of doxorubicin to combat hepatocellular carcinoma (HCC). Compared with monotherapy, the combination with TT46 vaccination and doxorubicin could significantly reduce microvessel counts and inhibit tumor angiogenesis. Enhanced immunization with TT46 for total six doses could induce long-term response maintenance with high anti-VEGF antibody titers in body. As a result, the combination with enhanced TT46 vaccination and doxorubicin significantly inhibited the HCC growth, and improved the survival rate of HCC-bearing mice in both of subcutaneous tumor model and lung metastasis model. In conclusion, the combined therapy with TT46 vaccination and doxorubicin has antitumor effects in both a prophylactic and therapeutic setting in a mouse model of H22 hepatocellular carcinoma.