title: 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.affiliation: State Key Laboratory of Biotherapy, West China Hospital and College of Life Science, Sichuan University, Keyuan Road 4, Chengdu, Sichuan 610041, People's Republic of China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Yao
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ding
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Ke
authors.initials: K
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Jiaming
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiancheng
authors.initials: X
authors.lastname: Chen
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
authors.forename: Jianrong
authors.initials: J
authors.lastname: Xu
authors.forename: Jumei
authors.initials: J
authors.lastname: Zhao
authors.forename: Ting
authors.initials: T
authors.lastname: Niu
authors.forename: Jiyan
authors.initials: J
authors.lastname: Liu
authors.forename: Qiu
authors.initials: Q
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wen
authors.forename: Jingmei
authors.initials: J
authors.lastname: Su
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Bu
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000256:Adenoviridae / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D000906:Antibodies / Q000097:blood; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008351:Mannans / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000517:prevention & control / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000276:immunology; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D000099152:Cadherin 5
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D015820:Cadherins; D019496:Cancer Vaccines; D004337:Drug Carriers; D008351:Mannans; D000099152:Cadherin 5