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Improved Anti-tumor Immunity Using Xenogenic Melanoma DNA Vaccines Combined with IL-12 and Ii-PADRE in Murine Melanoma
Liu Xianglei1, Zhang Lihong1, SunYunchun2, Steve Kay3, Wu Jiong1, 2, 3*
1Xinyuan Institute of Medicine and Biotechnology, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China; 2Richard J.Roberts Institute of Biotechnology, Yixing 214200, China; 3Yancheng Research Center of Tumor Biology and Targeted Therapy Engineering Technology, Yancheng 224005, China
Abstract: Active immunization with plasmid DNA encoding tyrosinase related protein 2 (TRP-2) and gp100 mediate anti-tumor immunity in the B16 murine melanoma model. TRP-2 and gp100 are highly expressed in both human and mouse melanoma. In this study， we used plasmid DNA encoding xenogenic (human) antigens to break tolerance to these antigens， since mouse gp100 (mgp100) and mouse TRP-2 (mTRP-2) are poorly immunogenic in mice. Immunization with plasmids encoding human gp100 (hgp100) and human TRP-2 (hTRP-2) showed significant protection in a B16F10 challenge model. Immunization with hgp100 and hTRP-2 combined with plasmid encoding Ii-PADRE (invariant Pan DR reactive epitope) and murine interleukin-12 caused regression of established B16F10 subcutaneous tumors. These results indicated that our approach of using intramuscular DNA vaccines encoding xenogenic antigens， combined with Ii-PADRE and IL-12 plasmid DNA could be an effective strategy against melanoma.
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