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抗人VEGF单抗的研制及对肿瘤生长及转移的抑制作用 |
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杨治华 石瑜琳 冉宇靓 王贵齐 刘 军 董志伟
摘 要 目的：为了确定人血管内皮细胞生长因子(Vascular Endothelial Growth Factor,VEGF)在肿瘤生长及转移中的作用。方法：利用DNA重组技术表达人VEGF，以其为抗原免疫Balb/c小鼠，应用杂交瘤技术获得14株稳定分泌抗VEGF单抗的杂交瘤细胞株。结果：ELISA测定所分泌的单抗只与VEGF特异结合，与EGF、FGF、PDGF、TGFα及TNF等均无交叉反应。以豚鼠皮肤血管通透性实验（Miles）、鸡胚绒毛尿囊膜血管形成实验（CAM）及人脐带静脉血管内皮细胞增殖实验（HuVEC）鉴定单抗的中和活性，其中9株具有中和活性。在小鼠自发乳癌肺转移模型中进行的抑瘤试验显示，单抗D11对乳癌原发瘤的抑制率达83.4%，对肺转移的抑制率为71.9%。结论：具有中和活性的VEGF单抗能抑制肿瘤的生长和转移。
关键词 VEGF 单克隆抗体 抑瘤试验
中国图书分类号 R392-33
Generation and characterization of monoclonal antibodies to human vascular endothelial growth factor 165 and the effect on primary and metastatic tumor growth of breast tumor
YANG Zhi-Hua，SHI Yu-Lin ，RAN Yu-Liang et al.
Cancer Institute, CAMS and PUMC, Beijing 100021
Abstract Objective: Monoclonal antibodies to human vascular endothelial growth factor (VEGF) were established and characterized to determine the role of VEGF in tumor and metastasis. Methods: Balb/c mice were immunized with recombinant hVEGF165 and the immunized spleen cells were fused with SP2/0-Ag14. Hybridomas cells secreting anti-VEGF McAbs were screened and characterized by ELISA, Western blot, and RIA. Neutralizing activity of anti-VEGF McAbs were identified by miles permeability assay (Miles), chicken chorioallantoic membranes angiogenesis assay (CAM) and human umbilical vein endothelial cell growth assay (HuVEC). The effect of neutralizing McAb-D11 on tumor growth was determined in IVT2MA-891 mouse model. Results: 14 hybridomas secreting anti-VEGF McAbs were established and 9 of the 14 hybridomas were neutralizing McAbs against hVEGF. Neutralizing McAb-D11 significantly inhibited both primary and metastatic tumor growth of mouse breast .Conclusion: These anti-VEGF McAbs provide a useful tool to study structure of VEGF and the role in tumor angiogenesis. These neutralizing McAbs against-VEGF may be potentially useful for clinical treatment of cancer.
Key words Tumor angioge[1] [2] 下一页
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