一种针对人 Delta 样配体 4 的抗体片段，用于抑制细胞增殖和血管新生。
An antibody fragment against human delta-like ligand-4 for inhibition of cell proliferation and neovascularization.
机构信息
a Department of Immunology, School of Medicine , Iran University of Medical Sciences , Tehran , Iran.
b Immunology Research Center (IRC), Iran University of Medical Sciences , Tehran , Iran.
出版信息
Immunopharmacol Immunotoxicol. 2018 Oct;40(5):368-374. doi: 10.1080/08923973.2018.1505907. Epub 2018 Sep 5.
OBJECTIVES
Angiogenesis targeting is an attractive approach for cancer treatment. Delta-like ligand 4 (DLL4) plays a pivotal role in neovascular development and its inhibitors have recently entered clinical trials for solid tumors. The aim of this study was to evaluate the possibilities of using anti-DLL4 antibody fragment as an angiogenesis maturation inhibitor.
MATERIALS AND METHODS
In this study, a DLL4-specific Nanobody, named 3Nb3, was selected and assessed by western blotting and internalization assays. Functional assessments included MTT, apoptosis, and chicken chorioallantoic membrane (CAM) assays.
RESULTS
Based on the results, 3Nb3 specifically binds to DLL4 and internalizes into MKN cell. Furthermore, 3Nb3 significantly inhibited the proliferation of cells and also neovascularization in the CAM.
CONCLUSIONS
These data demonstrated the potential of Nanobody for application in targeting DLL4. Our findings may provide a basis for the development of novel therapeutic techniques to inhibit growth and neovascularization of tumors.
目的
血管生成靶向是癌症治疗的一种有吸引力的方法。Delta-like 配体 4（DLL4）在新血管生成中发挥关键作用，其抑制剂最近已进入实体瘤的临床试验。本研究旨在评估抗 DLL4 抗体片段作为血管生成成熟抑制剂的可能性。
材料和方法
在这项研究中，选择了一种针对 DLL4 的纳米抗体，命名为 3Nb3，并通过 Western blot 和内化试验进行了评估。功能评估包括 MTT、凋亡和鸡胚尿囊膜（CAM）试验。
结果
根据结果，3Nb3 特异性结合 DLL4 并内化到 MKN 细胞中。此外，3Nb3 显著抑制了细胞的增殖和 CAM 中的新血管生成。
结论
这些数据表明纳米抗体在靶向 DLL4 中的应用潜力。我们的研究结果可能为开发抑制肿瘤生长和新血管生成的新型治疗技术提供依据。
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