Active Immunotherapy Of Cancer Induced By Oxidized Mannan-modified Recombinant Murine VE-cadherin Adenovirus

Targeting angiogenesis represents a new strategy for anticancer therapy. VE-cadherin (Vascular endothelial-cadherin) is an endothelial cell-specific adhesion molecule that plays an important role in endothelial cell biology. VE-cadherin may represent a potential target to prevent tumor neovascularization. During the past decade, antiangiogenesis therapy trials against VE-cadherin have been reported, mostly including passive immunization with monoclonal antibody. In this study, we hypothesized that breaking immune tolerance against self- VE-cadherin and inducing active immunization may be another promising approach to inhibit tumor angiogenesis and metastasis. It is well established that dendritic cells (DC) is a kind of potent antigen-presenting cell (APC). The high expression of mannan receptor(MR) make it possible to mediate recognization and uptake of antigens strongly, consequently, targetmg mannosylated antigens to APCs via MR in vivo or ex vivo has been investigated extensively for its ability to enhance immune responses. For this purpose, we evaluated an active immunization against self-VE-cadherin through an oxidized mannan-modifled immunogen source based on recombinant adenovirus.To test the hypothesis, we constructed a recombinant adenovirus encoding full cDNA sequence of mouse VE-cadherin and prepared a vaccination after modified by oxidized mannan (AdVEC-m). Inhibition of tumor-induced angiogenesis and tumor growth were observed by intraperitoneal transfer of AdVEC-m. High quantity of VE-cadherin-specific antibody was generated, CD8+-dependent CTL response for endothelial cells was also observed. The anti-tumor activity could be partly abrogated by depletion of CD4+ or CD8+ T lymphocytes. Angiogenesis was apparently reduced within the tumors, and the vascularization of alginate beads was also inhibited.Taken together, these findings suggested the oxidized mannan-modified AdVEC-m induced effectively antitumor response and may provide an active strategy for cancer therapy through the autoimmunity against the adhesive molecule associated with angiogenesis.