Antitumour immunity mediated by mannan-modified adenovirus vectors expressing VE-cadherin.
Antitumour immunity mediated by mannan-modified adenovirus vectors expressing VE-cadherin.
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DOI：
10.1016/j.vaccine.2011.03.109
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发表时间：
2011-06
期刊：
影响因子：
5.5
通讯作者：
Zhiwei Zhao;Yaqin Yao;Z. Ding;X. Chen;K. Xie;Yan Luo;Jiaming Zhang;Xiancheng Chen;Xiaohua Wu-Xiaoh
中科院分区：
文献类型：
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作者：
Zhiwei Zhao;Yaqin Yao;Z. Ding;X. Chen;K. Xie;Yan Luo;Jiaming Zhang;Xiancheng Chen;Xiaohua Wu-Xiaoh
抗血管生成是癌症治疗不可或缺的策略。血管内皮细胞钙粘附素(VE-cadherin，VE-cad)作为一种严格的内皮细胞特异性黏附分子，是一种很有前景的抗血管生成靶点。本研究采用甘露聚糖修饰的重组腺病毒载体携带VE-cad(AdVEC-m)，并探讨其作为抗肿瘤药物的可行性。VE-cad的免疫原性递送对小鼠肿瘤生长有明显的预防和治疗作用，延长了小鼠的生存时间。同时，免疫组织化学染色和藻酸盐包被微球实验显示肿瘤内血管生成明显减少。免疫印迹分析和酶联免疫吸附试验鉴定抗VE-cad抗体。用~(51)Cr释放法检测AdVEC-m处理小鼠脾细胞的VE-cad特异性T淋巴细胞毒性反应(CTL)。这些结果表明，甘露聚糖修饰能够增强抗原递送和免疫应答，免疫原性递送方式(AdVEC-m)有望为肿瘤免疫治疗提供一种有吸引力的疫苗策略。
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.