Full Length Research Paper

Protective antitumor activity induced by a fusion vaccine with murine beta-defensin2 and VE-cadherin in mouse models

Jian-rong Xu^{1, 2#}, Lian Wang^1#, Ju-mei Zhao^3#, Guo-qing Wang^1#, Gang Xie¹, Yang Wu¹, Hong-xia Li¹, Xiao-bo Du¹, Peng Diao¹, Han-suo Yang¹, Yan-jun Wen¹, Rui Wang¹, Hong-bing Wu¹, Yu-quan Wei¹, and Yong-sheng Wang¹*

¹State Key Laboratory of Biotherapy, West China Hospital, and School of Life Science, Sichuan University, Chengdu, PRC, China.

²Southwest University of Science and Technology, Mianyang City, Sichuan, 621010, PRC, China.

³Department of pharmacology, Medical College of yan’an University, Yan'an City, Shanxi, 716000, PRC, China.

*Corresponding author. E-mail: wangys@scu.edu.cn. Tel/Fax: 86-28-85164063.

^#These authors contributed equally to this work.

Abbreviations: mVE-cad, murine vascular endothelial cadherin; MBD2, murine beta-defensin2; pMBD2-mVE-cad, plasmid DNA encoding fusion gene with MBD2 and mVE-cad; pmVE-cad, plasmid DNA encoding mVE-cad; pMBD2, plasmid DNA encoding MBD2; iDC, immature dendritic cell; CTL, cytotoxic T lymphocyte.

Accepted 21 May, 2009

   Abstract

Targeting angiogenesis is an effective strategy for anticancer therapy. The vascular endothelial-cadherin (VE-cad) regulated angiogenesis is a potential target for anti-angiogenesis. Here, we develop a fusion vaccine plasmid DNA pSec-MBD2-VE-cad from VE-cad and murine beta defensin2 (MBD2) to induce immunity for cancer therapy. The expression and biological activity of fusion protein were detected in vitro. Anti-tumor effects and inhibition of angiogenesis via pSec-MBD2-VE-cad were investigated in mice model. The anti-VE-cad antibodies and cytotoxic T lymphocyte (CTL) responses were analyzed. Inhibition of tumor-induced angiogenesis and prolonged survival were shown in mice challenged with murine colon adenocarcinoma (CT26) or Murine fibrosarcoma cell line (MethA) after immunization with the fusion vaccine. Moreover, VE-cad-specific antibodies and specific T cell cytotoxicity were detected. The fusion vaccine based on self immune peptide Murine beta defensin2 (MBD2) and self antigen mVE-cad could induce autoimmunity and inhibit tumor growth, and thus there may be potential applications in cancer therapy.

Key words: Fusion vaccine, murine beta defensin2 (MBD2), murine vascular endothelial-cadherin (mVE-cad), antigen targeting, anti-angiogenesis.