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.
Vaccine. 2011 Jun 6;29(25):4218-24. doi: 10.1016/j.vaccine.2011.03.109. Epub 2011 Apr 15.
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.
抗血管生成是癌症治疗中不可或缺的策略。血管内皮钙黏蛋白（VE-cadherin，VE-cad）作为一种严格的内皮细胞特异性黏附分子，是一种很有前途的抗血管生成靶点。在这项研究中，我们使用经过甘露聚糖修饰的重组腺病毒载体来递送 VE-cad（AdVEC-m），并试图探索其在小鼠癌症模型中作为抗肿瘤药物的可行性。VE-cad 的免疫递送导致肿瘤生长明显的预防和治疗性抑制，并延长了小鼠的生存时间。同时，通过免疫组化染色和体内包被藻酸盐珠测定，肿瘤内的血管生成明显下降。通过 Western blot 分析和酶联免疫吸附试验（ELISA）检测到抗 VE-cad 抗体。通过铬（51Cr）释放试验检测来自 AdVEC-m 处理的小鼠脾细胞的 VE-cad 特异性 T 淋巴细胞细胞毒性反应（CTL）。这些结果表明，甘露聚糖修饰能够增强抗原递呈和免疫反应，免疫递呈（AdVEC-m）的方式有望为癌症免疫治疗提供一种有吸引力的疫苗策略。
