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

Abstract

Targeting angiogenesis is an effective strategy for anticancer therapy. The vascular endothelialcadherin (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.