Antitumour immunity mediated by mannan-modified adenovirus vectors expressing VE-cadherin.

Abstract

Anti-angiogenesis represents an indispensible strategy for cancer therapy. As a strictly endothelial-specific adhesion molecule, vascular endothelial cadherin (VE-cadherin, VE-cad) is a promising anti-angiogenesis target. In this study a recombinant adenovirus vector modified with mannan was used to deliver VE-cad (AdVEC-m) and we tried to explore its feasibility as an antitumour agent in mouse cancer models. The immunogenic delivery of VE-cad resulted in obvious prophylactic and therapeutic inhibition of tumour growth and prolonged survival in mice. In the meantime angiogenesis declined apparently within the tumours measured by immunohistochemistry staining and coated alginate bead assay in vivo. Anti-VE-cad antibodies were identified by western blot analysis and enzyme-linked immunosorbent assay (ELISA). VE-cad-specific T lymphocyte cytotoxicity responses (CTL) were detected by chromium (51Cr) release assay of splenocytes from AdVEC-m treated mice. These results demonstrate that mannan modification is able to enhance antigen delivery and immune responses, and the way of immunogenic delivery (AdVEC-m) is expected to provide an attractive vaccine strategy for cancer immunotherapy.

• Authors: Zhiwei Zhao, Yaqin Yao, Zhenyu Ding, Xi Chen, Ke Xie, Yan Luo, Jiaming Zhang, Xiancheng Chen, Xiaohua Wu, Jianrong Xu, Jumei Zhao, Ting Niu, Jiyan Liu, Qiu Li, Wei Zhang, Yanjun Wen, Jingmei Su, Bing Hu, Hong Bu, Yuquan Wei, Yang Wu
• Journal: Vaccine (Vaccine) Vol. 29 Issue 25 Pg. 4218-24 (Jun 06 2011) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 21497630 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies
• Antigens, CD
• Cadherins
• Cancer Vaccines
• Drug Carriers
• Mannans
• cadherin 5

Topics

• Adenoviridae (chemistry, genetics)
• Animals
• Antibodies (blood)
• Antigens, CD (genetics, immunology)
• Blotting, Western
• Cadherins (genetics, immunology)
• Cancer Vaccines (genetics, immunology)
• Cytotoxicity Tests, Immunologic
• Cytotoxicity, Immunologic
• Drug Carriers (chemistry)
• Female
• Genetic Vectors
• Humans
• Immunotherapy (methods)
• Mannans (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Neoplasms (prevention & control, therapy)
• Neovascularization, Pathologic (immunology)
• Survival Analysis
• T-Lymphocytes, Cytotoxic (immunology)